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Sample records for acute rodent malaria

  1. Rodent malaria parasites : genome organization & comparative genomics

    NARCIS (Netherlands)

    Kooij, Taco W.A.

    2006-01-01

    The aim of the studies described in this thesis was to investigate the genome organization of rodent malaria parasites (RMPs) and compare the organization and gene content of the genomes of RMPs and the human malaria parasite P. falciparum. The release of the complete genome sequence of P. falciparu

  2. Rodent malaria parasites : genome organization & comparative genomics

    NARCIS (Netherlands)

    Kooij, Taco W.A.

    2006-01-01

    The aim of the studies described in this thesis was to investigate the genome organization of rodent malaria parasites (RMPs) and compare the organization and gene content of the genomes of RMPs and the human malaria parasite P. falciparum. The release of the complete genome sequence of P.

  3. Chemotherapy of Rodent Malaria. Part 1.

    Science.gov (United States)

    1986-09-01

    nave bene’o rried out and talc screeningisr- -x , -doj to all of te s rainz of rodent malaria held in our A : ,-W ",2h5ni q uV wn i .’n re. .,cenLI y...hepitocytes. After two hours incubation, 1 ml of MEM with ’C, anti biotics and cortisone is added to each of the ,t re . r,,,-,I r o t o i *!.,1r- S 1- a :I

  4. VEGF Promotes Malaria-Associated Acute Lung Injury in Mice

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    Carapau, Daniel; Pena, Ana C.; Ataíde, Ricardo; Monteiro, Carla A. A.; Félix, Nuno; Costa-Silva, Artur; Marinho, Claudio R. F.; Dias, Sérgio; Mota, Maria M.

    2010-01-01

    The spectrum of the clinical presentation and severity of malaria infections is broad, ranging from uncomplicated febrile illness to severe forms of disease such as cerebral malaria (CM), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), pregnancy-associated malaria (PAM) or severe anemia (SA). Rodent models that mimic human CM, PAM and SA syndromes have been established. Here, we show that DBA/2 mice infected with P. berghei ANKA constitute a new model for malaria-associated ALI. Up to 60% of the mice showed dyspnea, airway obstruction and hypoxemia and died between days 7 and 12 post-infection. The most common pathological findings were pleural effusion, pulmonary hemorrhage and edema, consistent with increased lung vessel permeability, while the blood-brain barrier was intact. Malaria-associated ALI correlated with high levels of circulating VEGF, produced de novo in the spleen, and its blockage led to protection of mice from this syndrome. In addition, either splenectomization or administration of the anti-inflammatory molecule carbon monoxide led to a significant reduction in the levels of sera VEGF and to protection from ALI. The similarities between the physiopathological lesions described here and the ones occurring in humans, as well as the demonstration that VEGF is a critical host factor in the onset of malaria-associated ALI in mice, not only offers important mechanistic insights into the processes underlying the pathology related with malaria but may also pave the way for interventional studies. PMID:20502682

  5. Mitochondrial genes support a common origin of rodent malaria parasites and Plasmodium falciparum's relatives infecting great apes

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    Blanquart Samuel

    2011-03-01

    Full Text Available Abstract Background Plasmodium falciparum is responsible for the most acute form of human malaria. Most recent studies demonstrate that it belongs to a monophyletic lineage specialized in the infection of great ape hosts. Several other Plasmodium species cause human malaria. They all belong to another distinct lineage of parasites which infect a wider range of primate species. All known mammalian malaria parasites appear to be monophyletic. Their clade includes the two previous distinct lineages of parasites of primates and great apes, one lineage of rodent parasites, and presumably Hepatocystis species. Plasmodium falciparum and great ape parasites are commonly thought to be the sister-group of all other mammal-infecting malaria parasites. However, some studies supported contradictory origins and found parasites of great apes to be closer to those of rodents, or to those of other primates. Results To distinguish between these mutually exclusive hypotheses on the origin of Plasmodium falciparum and its great ape infecting relatives, we performed a comprehensive phylogenetic analysis based on a data set of three mitochondrial genes from 33 to 84 malaria parasites. We showed that malarial mitochondrial genes have evolved slowly and are compositionally homogeneous. We estimated their phylogenetic relationships using Bayesian and maximum-likelihood methods. Inferred trees were checked for their robustness to the (i site selection, (ii assumptions of various probabilistic models, and (iii taxon sampling. Our results robustly support a common ancestry of rodent parasites and Plasmodium falciparum's relatives infecting great apes. Conclusions Our results refute the most common view of the origin of great ape malaria parasites, and instead demonstrate the robustness of a less well-established phylogenetic hypothesis, under which Plasmodium falciparum and its relatives infecting great apes are closely related to rodent parasites. This study sheds light

  6. Severe acute renal failure in malaria.

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    Mehta K

    2001-01-01

    Full Text Available BACKGROUND: We have noticed a recent rise in the incidence and severity of acute renal failure (ARF in malaria. AIM: To study the incidence, severity and outcome of ARF in malaria. SETTING and DESIGN: It is a retrospective analysis of data of one year from a tertiary medical centre in a metropolitan city. MATERIALS AND METHODS: Patients with ARF and smear positive malaria were evaluated. STATISTICAL ANALYSIS: Results were expressed as mean, range and standard deviation. RESULTS: Out of 402 detected smear positive malaria, 24 had ARF. Eighteen were of the age group 21-40 years. Plasmodium falciparum (PF was detected in 16, Plasmodium vivax in three, and mixed infection in five. Non-oliguric ARF was seen in 14. Eighteen showed severe ARF (Serum creatinine >5 mg%. Twenty-two patients needed dialysis. Prolonged ARF lasting for 2-6 weeks was seen in eight. Seventeen patients recovered completely, while seven showed fatal combination of disseminated intravascular coagulation (DIC, acute respiratory distress syndrome (ARDS, severe ARF and PF malaria. No response was seen to chloroquine and artesunate given alone and twenty patients required quinine. CONCLUSION: ARF necessitating dialysis was seen in 92% of patients with ARF in malaria. PF infection, severe ARF, DIC and ARDS were poor prognostic factors. Resistance was noted to both chloroquine and artesunate.

  7. The relevance of non-human primate and rodent malaria models for humans

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    Riley Eleanor

    2011-02-01

    Full Text Available Abstract At the 2010 Keystone Symposium on "Malaria: new approaches to understanding Host-Parasite interactions", an extra scientific session to discuss animal models in malaria research was convened at the request of participants. This was prompted by the concern of investigators that skepticism in the malaria community about the use and relevance of animal models, particularly rodent models of severe malaria, has impacted on funding decisions and publication of research using animal models. Several speakers took the opportunity to demonstrate the similarities between findings in rodent models and human severe disease, as well as points of difference. The variety of malaria presentations in the different experimental models parallels the wide diversity of human malaria disease and, therefore, might be viewed as a strength. Many of the key features of human malaria can be replicated in a variety of nonhuman primate models, which are very under-utilized. The importance of animal models in the discovery of new anti-malarial drugs was emphasized. The major conclusions of the session were that experimental and human studies should be more closely linked so that they inform each other, and that there should be wider access to relevant clinical material.

  8. Of mice and women: rodent models of placental malaria

    DEFF Research Database (Denmark)

    Hviid, Lars; Marinho, Claudio R F; Staalsoe, Trine

    2010-01-01

    Pregnant women are at increased malaria risk. The infections are characterized by placental accumulation of infected erythrocytes (IEs) with adverse consequences for mother and baby. Placental IE sequestration in the intervillous space is mediated by variant surface antigens (VSAs) selectively ex...

  9. The Plasmodium apicoplast genome: conserved structure and close relationship of P. ovale to rodent malaria parasites.

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    Arisue, Nobuko; Hashimoto, Tetsuo; Mitsui, Hideya; Palacpac, Nirianne M Q; Kaneko, Akira; Kawai, Satoru; Hasegawa, Masami; Tanabe, Kazuyuki; Horii, Toshihiro

    2012-09-01

    Apicoplast, a nonphotosynthetic plastid derived from secondary symbiotic origin, is essential for the survival of malaria parasites of the genus Plasmodium. Elucidation of the evolution of the apicoplast genome in Plasmodium species is important to better understand the functions of the organelle. However, the complete apicoplast genome is available for only the most virulent human malaria parasite, Plasmodium falciparum. Here, we obtained the near-complete apicoplast genome sequences from eight Plasmodium species that infect a wide variety of vertebrate hosts and performed structural and phylogenetic analyses. We found that gene repertoire, gene arrangement, and other structural attributes were highly conserved. Phylogenetic reconstruction using 30 protein-coding genes of the apicoplast genome inferred, for the first time, a close relationship between P. ovale and rodent parasites. This close relatedness was robustly supported using multiple evolutionary assumptions and models. The finding suggests that an ancestral host switch occurred between rodent and human Plasmodium parasites.

  10. Loss of cellular immune reactivity during acute Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Hviid, L; Theander, T G; Abu-Zeid, Y A;

    1991-01-01

    Sixteen patients suffering from acute Plasmodium falciparum malaria were studied. All were residents of an area of unstable malaria-transmission in Eastern Sudan. Blood-samples were drawn at diagnosis, and 7 and 30 days later. Blood-samples from thirteen donors, drawn outside the malaria...... convalescence. Five donors examined by fluorescence-activated cell sorting (FACS) showed no increase in surface expression of IL-2 receptor on peripheral lymphocytes. The data indicate that acute P. falciparum malaria causes a depletion of antigen-reactive T-cells from the peripheral circulation, probably due...

  11. Loss of cellular immune reactivity during acute Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Hviid, L; Theander, T G; Abu-Zeid, Y A

    1991-01-01

    Sixteen patients suffering from acute Plasmodium falciparum malaria were studied. All were residents of an area of unstable malaria-transmission in Eastern Sudan. Blood-samples were drawn at diagnosis, and 7 and 30 days later. Blood-samples from thirteen donors, drawn outside the malaria...... convalescence. Five donors examined by fluorescence-activated cell sorting (FACS) showed no increase in surface expression of IL-2 receptor on peripheral lymphocytes. The data indicate that acute P. falciparum malaria causes a depletion of antigen-reactive T-cells from the peripheral circulation, probably due...

  12. Acute kidney injury in imported Plasmodium falciparum malaria

    NARCIS (Netherlands)

    L.C. Koopmans (Liese); M.E. van Wolfswinkel (Marlies); D.A. Hesselink (Dennis); E.J. Hoorn (Ewout); R. Koelewijn (Rob); J.J. van Hellemond (Jaap); P.J.J. van Genderen (Perry)

    2015-01-01

    textabstractBackground: Acute kidney injury (AKI) is a known complication of malaria, and is reported to occur in up to 40 % of adult patients with a severe Plasmodium falciparum infection in endemic regions. To gain insight in the incidence and risk factors of AKI in imported P. falciparum malaria,

  13. Acute kidney injury in imported Plasmodium falciparum malaria

    NARCIS (Netherlands)

    L.C. Koopmans, L.C. (Liese); M.E. van Wolfswinkel (Marlies); D.A. Hesselink (Dennis); E.J. Hoorn (Ewout); R. Koelewijn (Rob); J.J. van Hellemond (Jaap); P.J. van Genderen (P.)

    2015-01-01

    textabstractBackground: Acute kidney injury (AKI) is a known complication of malaria, and is reported to occur in up to 40 % of adult patients with a severe Plasmodium falciparum infection in endemic regions. To gain insight in the incidence and risk factors of AKI in imported P. falciparum malaria,

  14. Competitive release and facilitation of drug-resistant parasites after therapeutic chemotherapy in a rodent malaria model

    Science.gov (United States)

    Wargo, A.R.; Huijben, S.; De Roode, J. C.; Shepherd, J.; Read, A.F.

    2007-01-01

    Malaria infections frequently consist of mixtures of drug-resistant and drug-sensitive parasites. If crowding occurs, where clonal population densities are suppressed by the presence of coinfecting clones, removal of susceptible clones by drug treatment could allow resistant clones to expand into the newly vacated niche space within a host. Theoretical models show that, if such competitive release occurs, it can be a potent contributor to the strength of selection, greatly accelerating the rate at which resistance spreads in a population. A variety of correlational field data suggest that competitive release could occur in human malaria populations, but direct evidence cannot be ethically obtained from human infections. Here we show competitive release after pyrimethamine curative chemotherapy of acute infections of the rodent malaria Plasmodium chabaudi in laboratory mice. The expansion of resistant parasite numbers after treatment resulted in enhanced transmission-stage densities. After the elimination or near-elimination of sensitive parasites, the number of resistant parasites increased beyond that achieved when a competitor had never been present. Thus, a substantial competitive release occurred, markedly elevating the fitness advantages of drug resistance above those arising from survival alone. This finding may explain the rapid spread of drug resistance and the subsequently brief useful lifespans of some antimalarial drugs. In a second experiment, where subcurative chemotherapy was administered, the resistant clone was only partly released from competitive suppression and experienced a restriction in the size of its expansion after treatment. This finding raises the prospect of harnessing in-host ecology to slow the spread of drug resistance. ?? 2007 by The National Academy of Sciences of the USA.

  15. Enzymatic Characterization of Recombinant Food Vacuole Plasmepsin 4 from the Rodent Malaria Parasite Plasmodium berghei.

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    Peng Liu

    Full Text Available The rodent malaria parasite Plasmodium berghei is a practical model organism for experimental studies of human malaria. Plasmepsins are a class of aspartic proteinase isoforms that exert multiple pathological effects in malaria parasites. Plasmepsins residing in the food vacuole (FV of the parasite hydrolyze hemoglobin in red blood cells. In this study, we cloned PbPM4, the FV plasmepsin gene of P. berghei that encoded an N-terminally truncated pro-segment and the mature enzyme from genomic DNA. We over-expressed this PbPM4 zymogen as inclusion bodies (IB in Escherichia coli, and purified the protein following in vitro IB refolding. Auto-maturation of the PbPM4 zymogen to mature enzyme was carried out at pH 4.5, 5.0, and 5.5. Interestingly, we found that the PbPM4 zymogen exhibited catalytic activity regardless of the presence of the pro-segment. We determined the optimal catalytic conditions for PbPM4 and studied enzyme kinetics on substrates and inhibitors of aspartic proteinases. Using combinatorial chemistry-based peptide libraries, we studied the active site preferences of PbPM4 at subsites S1, S2, S3, S1', S2' and S3'. Based on these results, we designed and synthesized a selective peptidomimetic compound and tested its inhibition of PbPM4, seven FV plasmepsins from human malaria parasites, and human cathepsin D (hcatD. We showed that this compound exhibited a >10-fold selectivity to PbPM4 and human malaria parasite plasmepsin 4 orthologs versus hcatD. Data from this study furthesr our understanding of enzymatic characteristics of the plasmepsin family and provides leads for anti-malarial drug design.

  16. The utility of Plasmodium berghei as a rodent model for anti-merozoite malaria vaccine assessment.

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    Goodman, Anna L; Forbes, Emily K; Williams, Andrew R; Douglas, Alexander D; de Cassan, Simone C; Bauza, Karolis; Biswas, Sumi; Dicks, Matthew D J; Llewellyn, David; Moore, Anne C; Janse, Chris J; Franke-Fayard, Blandine M; Gilbert, Sarah C; Hill, Adrian V S; Pleass, Richard J; Draper, Simon J

    2013-01-01

    Rodent malaria species Plasmodium yoelii and P. chabaudi have been widely used to validate vaccine approaches targeting blood-stage merozoite antigens. However, increasing data suggest the P. berghei rodent malaria may be able to circumvent vaccine-induced anti-merozoite responses. Here we confirm a failure to protect against P. berghei, despite successful antibody induction against leading merozoite antigens using protein-in-adjuvant or viral vectored vaccine delivery. No subunit vaccine approach showed efficacy in mice following immunization and challenge with the wild-type P. berghei strains ANKA or NK65, or against a chimeric parasite line encoding a merozoite antigen from P. falciparum. Protection was not improved in knockout mice lacking the inhibitory Fc receptor CD32b, nor against a Δsmac P. berghei parasite line with a non-sequestering phenotype. An improved understanding of the mechanisms responsible for protection, or failure of protection, against P. berghei merozoites could guide the development of an efficacious vaccine against P. falciparum.

  17. The Plasmodium PHIST and RESA-Like Protein Families of Human and Rodent Malaria Parasites.

    Science.gov (United States)

    Moreira, Cristina K; Naissant, Bernina; Coppi, Alida; Bennett, Brandy L; Aime, Elena; Franke-Fayard, Blandine; Janse, Chris J; Coppens, Isabelle; Sinnis, Photini; Templeton, Thomas J

    2016-01-01

    The phist gene family has members identified across the Plasmodium genus, defined by the presence of a domain of roughly 150 amino acids having conserved aromatic residues and an all alpha-helical structure. The family is highly amplified in P. falciparum, with 65 predicted genes in the genome of the 3D7 isolate. In contrast, in the rodent malaria parasite P. berghei 3 genes are identified, one of which is an apparent pseudogene. Transcripts of the P. berghei phist genes are predominant in schizonts, whereas in P. falciparum transcript profiles span different asexual blood stages and gametocytes. We pursued targeted disruption of P. berghei phist genes in order to characterize a simplistic model for the expanded phist gene repertoire in P. falciparum. Unsuccessful attempts to disrupt P. berghei PBANKA_114540 suggest that this phist gene is essential, while knockout of phist PBANKA_122900 shows an apparent normal progression and non-essential function throughout the life cycle. Epitope-tagging of P. falciparum and P. berghei phist genes confirmed protein export to the erythrocyte cytoplasm and localization with a punctate pattern. Three P. berghei PEXEL/HT-positive exported proteins exhibit at least partial co-localization, in support of a common vesicular compartment in the cytoplasm of erythrocytes infected with rodent malaria parasites.

  18. Malaria induced acute renal failure: A single center experience

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    Kanodia K

    2010-01-01

    Full Text Available Malaria has protean clinical manifestations and renal complications, particularly acute renal failure that could be life threatening. To evaluate the incidence, clinical profile, out-come and predictors of mortality in patients with malarial acute renal failure, we retrospectively studied the last two years records of malaria induced acute renal failure in patients with peripheral smear positive for malarial parasites. One hundred (10.4% (63 males, 37 females malaria induced acute renal failure amongst 958 cases of acute renal failure were evaluated. Plasmodium (P. falciparum was reported in 85%, P. vivax in 2%, and both in 13% patients. The mean serum creatinine was 9.2 ± 4.2 mg%, and oligo/anuria was present in 82%; 78% of the patients required hemodialysis. Sixty four percent of the patients recovered completely, 10% incompletely, and 5% developed chronic kidney failure; mortality occurred in 21% of the patients. Low hemoglobin, oligo/anuria on admission, hyperbilirubinemia, cerebral malaria, disseminated intravascular coa-gulation, and high serum creatinine were the main predictors of mortality. We conclude that ma-laria is associated with acute renal failure, which occurs most commonly in plasmodium falci-parum infected patients. Early diagnosis and prompt dialysis with supportive management can reduce morality and enhance recovery of renal function.

  19. Acute cerebellar ataxia: A neurological manifestation in malaria

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    Peddametla Shravan Kumar

    2014-01-01

    Full Text Available Malaria is a vector-borne disease transmitted by the bite of an infected female anopheles mosquito presents with varied clinical manifestations. Neurological manifestations include headaches, confusion, convulsions, hemiplegia, ataxia, cerebral palsy, cortical blindness, and Guillain-Barre syndrome (GBS. We are presenting a case report of acute cerebellar ataxia in a 20-year-old male patient who presented with fever and positive for Plasmodium vivax and Plasmodium falciparum malaria antibodies.

  20. A comprehensive evaluation of rodent malaria parasite genomes and gene expression

    KAUST Repository

    Otto, Thomas D

    2014-10-30

    Background: Rodent malaria parasites (RMP) are used extensively as models of human malaria. Draft RMP genomes have been published for Plasmodium yoelii, P. berghei ANKA (PbA) and P. chabaudi AS (PcAS). Although availability of these genomes made a significant impact on recent malaria research, these genomes were highly fragmented and were annotated with little manual curation. The fragmented nature of the genomes has hampered genome wide analysis of Plasmodium gene regulation and function. Results: We have greatly improved the genome assemblies of PbA and PcAS, newly sequenced the virulent parasite P. yoelii YM genome, sequenced additional RMP isolates/lines and have characterized genotypic diversity within RMP species. We have produced RNA-seq data and utilized it to improve gene-model prediction and to provide quantitative, genome-wide, data on gene expression. Comparison of the RMP genomes with the genome of the human malaria parasite P. falciparum and RNA-seq mapping permitted gene annotation at base-pair resolution. Full-length chromosomal annotation permitted a comprehensive classification of all subtelomeric multigene families including the `Plasmodium interspersed repeat genes\\' (pir). Phylogenetic classification of the pir family, combined with pir expression patterns, indicates functional diversification within this family. Conclusions: Complete RMP genomes, RNA-seq and genotypic diversity data are excellent and important resources for gene-function and post-genomic analyses and to better interrogate Plasmodium biology. Genotypic diversity between P. chabaudi isolates makes this species an excellent parasite to study genotype-phenotype relationships. The improved classification of multigene families will enhance studies on the role of (variant) exported proteins in virulence and immune evasion/modulation.

  1. Transformation of the rodent malaria parasite Plasmodium chabaudi and generation of a stable fluorescent line PcGFPCON

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    Reece Sarah E

    2008-09-01

    Full Text Available Abstract Background The rodent malaria parasite Plasmodium chabaudi has proven of great value in the analysis of fundamental aspects of host-parasite-vector interactions implicated in disease pathology and parasite evolutionary ecology. However, the lack of gene modification technologies for this model has precluded more direct functional studies. Methods The development of in vitro culture methods to yield P. chabaudi schizonts for transfection and conditions for genetic modification of this rodent malaria model are reported. Results Independent P. chabaudi gene-integrant lines that constitutively express high levels of green fluorescent protein throughout their life cycle have been generated. Conclusion Genetic modification of P. chabaudi is now possible. The production of genetically distinct reference lines offers substantial advances to our understanding of malaria parasite biology, especially interactions with the immune system during chronic infection.

  2. High diversity of West African bat malaria parasites and a tight link with rodent Plasmodium taxa.

    Science.gov (United States)

    Schaer, Juliane; Perkins, Susan L; Decher, Jan; Leendertz, Fabian H; Fahr, Jakob; Weber, Natalie; Matuschewski, Kai

    2013-10-22

    As the only volant mammals, bats are captivating for their high taxonomic diversity, for their vital roles in ecosystems--particularly as pollinators and insectivores--and, more recently, for their important roles in the maintenance and transmission of zoonotic viral diseases. Genome sequences have identified evidence for a striking expansion of and positive selection in gene families associated with immunity. Bats have also been known to be hosts of malaria parasites for over a century, and as hosts, they possess perhaps the most phylogenetically diverse set of hemosporidian genera and species. To provide a molecular framework for the study of these parasites, we surveyed bats in three remote areas of the Upper Guinean forest ecosystem. We detected four distinct genera of hemosporidian parasites: Plasmodium, Polychromophilus, Nycteria, and Hepatocystis. Intriguingly, the two species of Plasmodium in bats fall within the clade of rodent malaria parasites, indicative of multiple host switches across mammalian orders. We show that Nycteria species form a very distinct phylogenetic group and that Hepatocystis parasites display an unusually high diversity and prevalence in epauletted fruit bats. The diversity and high prevalence of novel lineages of chiropteran hemosporidians underscore the exceptional position of bats among all other mammalian hosts of hemosporidian parasites and support hypotheses of pathogen tolerance consistent with the exceptional immunology of bats.

  3. High diversity of West African bat malaria parasites and a tight link with rodent Plasmodium taxa

    Science.gov (United States)

    Schaer, Juliane; Perkins, Susan L.; Decher, Jan; Leendertz, Fabian H.; Fahr, Jakob; Weber, Natalie; Matuschewski, Kai

    2013-01-01

    As the only volant mammals, bats are captivating for their high taxonomic diversity, for their vital roles in ecosystems—particularly as pollinators and insectivores—and, more recently, for their important roles in the maintenance and transmission of zoonotic viral diseases. Genome sequences have identified evidence for a striking expansion of and positive selection in gene families associated with immunity. Bats have also been known to be hosts of malaria parasites for over a century, and as hosts, they possess perhaps the most phylogenetically diverse set of hemosporidian genera and species. To provide a molecular framework for the study of these parasites, we surveyed bats in three remote areas of the Upper Guinean forest ecosystem. We detected four distinct genera of hemosporidian parasites: Plasmodium, Polychromophilus, Nycteria, and Hepatocystis. Intriguingly, the two species of Plasmodium in bats fall within the clade of rodent malaria parasites, indicative of multiple host switches across mammalian orders. We show that Nycteria species form a very distinct phylogenetic group and that Hepatocystis parasites display an unusually high diversity and prevalence in epauletted fruit bats. The diversity and high prevalence of novel lineages of chiropteran hemosporidians underscore the exceptional position of bats among all other mammalian hosts of hemosporidian parasites and support hypotheses of pathogen tolerance consistent with the exceptional immunology of bats. PMID:24101466

  4. Signatures of malaria-associated pathology revealed by high-resolution whole-blood transcriptomics in a rodent model of malaria

    Science.gov (United States)

    Lin, Jing-wen; Sodenkamp, Jan; Cunningham, Deirdre; Deroost, Katrien; Tshitenge, Tshibuayi Christine; McLaughlin, Sarah; Lamb, Tracey J.; Spencer-Dene, Bradley; Hosking, Caroline; Ramesar, Jai; Janse, Chris J.; Graham, Christine; O’Garra, Anne; Langhorne, Jean

    2017-01-01

    The influence of parasite genetic factors on immune responses and development of severe pathology of malaria is largely unknown. In this study, we performed genome-wide transcriptomic profiling of mouse whole blood during blood-stage infections of two strains of the rodent malaria parasite Plasmodium chabaudi that differ in virulence. We identified several transcriptomic signatures associated with the virulent infection, including signatures for platelet aggregation, stronger and prolonged anemia and lung inflammation. The first two signatures were detected prior to pathology. The anemia signature indicated deregulation of host erythropoiesis, and the lung inflammation signature was linked to increased neutrophil infiltration, more cell death and greater parasite sequestration in the lungs. This comparative whole-blood transcriptomics profiling of virulent and avirulent malaria shows the validity of this approach to inform severity of the infection and provide insight into pathogenic mechanisms. PMID:28155887

  5. Acute Blast Injury Reduces Brain Abeta in Two Rodent Species

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    Rita eDe Gasperi

    2012-12-01

    Full Text Available Blast-induced traumatic brain injury (TBI has been a major cause of morbidity and mortality in the conflicts in Iraq and Afghanistan. How the primary blast wave affects the brain is not well understood. In particular, it is unclear whether blast injures the brain through mechanisms similar to those found in non-blast closed impact injuries (nbTBI. The β-amyloid (Aβ peptide associated with the development of Alzheimer’s disease (AD is elevated acutely following TBI in humans as well as in experimental animal models of nbTBI. We examined levels of brain Aβ following experimental blast injury using enzyme-linked immunosorbent assays for Aβ 40 and 42. In both rat and mouse models of blast injury, rather than being increased, endogenous rodent brain Aβ levels were decreased acutely following injury. Levels of the amyloid precursor protein (APP were increased following blast exposure although there was no evidence of axonal pathology based on APP immunohistochemical staining. Unlike the findings in nbTBI animal models, levels of the β-secretase, BACE-1, and the γ-secretase component presenilin-1 were unchanged following blast exposure. These studies have implications for understanding the nature of blast injury to the brain. They also suggest that strategies aimed at lowering Aβ production may not be effective for treating acute blast injury to the brain.

  6. Allicin enhances host pro-inflammatory immune responses and protects against acute murine malaria infection

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    Feng Yonghui

    2012-08-01

    Full Text Available Abstract Background During malaria infection, multiple pro-inflammatory mediators including IFN-γ, TNF and nitric oxide (NO play a crucial role in the protection against the parasites. Modulation of host immunity is an important strategy to improve the outcome of malaria infection. Allicin is the major biologically active component of garlic and shows anti-microbial activity. Allicin is also active against protozoan parasites including Plasmodium, which is thought to be mediated by inhibiting cysteine proteases. In this study, the immunomodulatory activities of allicin were assessed during acute malaria infection using a rodent malaria model Plasmodium yoelii 17XL. Methods To determine whether allicin modulates host immune responses against malaria infection, mice were treated with allicin after infection with P. yoelii 17XL. Mortality was checked daily and parasitaemia was determined every other day. Pro-inflammatory mediators and IL-4 were quantified by ELISA, while NO level was determined by the Griess method. The populations of dendritic cells (DCs, macrophages, CD4+ T and regulatory T cells (Treg were assessed by FACS. Results Allicin reduced parasitaemia and prolonged survival of the host in a dose-dependent manner. This effect is at least partially due to improved host immune responses. Results showed that allicin treatment enhanced the production of pro-inflammatory mediators such as IFN-γ, TNF, IL-12p70 and NO. The absolute numbers of CD4+ T cells, DCs and macrophages were significantly higher in allicin-treated mice. In addition, allicin promoted the maturation of CD11c+ DCs, whereas it did not cause major changes in IL-4 and the level of anti-inflammatory cytokine IL-10. Conclusions Allicin could partially protect host against P. yoelii 17XL through enhancement of the host innate and adaptive immune responses.

  7. Molecular cloning and biochemical characterization of iron superoxide dismutase from the rodent malaria parasite Plasmodium vinckei.

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    Prakash, Kirtika; Goyal, Manish; Soni, Awakash; Siddiqui, Arif Jamal; Bhardwaj, Jyoti; Puri, Sunil K

    2014-12-01

    Plasmodium parasite utilizes superoxide dismutase family proteins to limit the toxicity of reactive oxygen species, such as produced through hemoglobin degradation. These proteins play an important role in parasite survival during intra-erythrocytic phase. We have identified, and biochemically characterized a putative iron dependent superoxide dismutase from rodent malaria parasite Plasmodium vinckei (PvSOD1). The recombinant PvSOD1 protein was purified to homogeneity through a combination of affinity and gel filtration chromatography. Crosslinking, Native-PAGE and FPLC gel filtration analyses documented that PvSOD1 exists as a dimer in solution, a common feature shared by other Fe-SODs. PvSOD1 is cytosolic in localization and its expression is comparatively higher during trophozoite as compared to that of ring and schizont stages. Enzymatic activity of recombinant PvSOD1 was validated using conventional zymogram analyses and xanthine-xanthine oxidase system. Under optimal conditions, PvSOD1 was highly active and catalyzed the dismutation of superoxide radicals. Furthermore, PvSOD1 showed activity over a broad range of pH and temperature. Inhibition studies suggested that PvSOD1 was inactivated by hydrogen peroxide, and peroxynitrite, but not by cyanide and azide. Since, PvSOD1 plays a central role in oxidative defense mechanism, therefore, characterization of PvSOD1 will be exploited in the screening of new superoxide dismutase inhibitors for their antimalarial activity. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  8. Cloning, expression and functional characterization of heme detoxification protein (HDP) from the rodent malaria parasite Plasmodium vinckei.

    Science.gov (United States)

    Soni, Awakash; Goyal, Manish; Prakash, Kirtika; Bhardwaj, Jyoti; Siddiqui, Arif Jamal; Puri, Sunil K

    2015-07-15

    Malaria parasite resides within the host red blood cells, where it degrades vast amount of haemoglobin. During haemoglobin degradation, toxic free heme is liberated which subsequently gets converted into hemozoin. This process is facilitated by action of various proteins viz. heme detoxification protein (HDP), and histidine rich proteins II and III (HRP II & III). Out of these, HDP is the most potent in hemozoin formation and plays indispensible role for parasite survival. Despite this, the detailed study of HDP from rodent and simian parasite has not been performed till date. Here, we have cloned and sequenced hdp gene from different malaria parasites Plasmodium vinckei, Plasmodium yoelii, Plasmodium knowlesi, and Plasmodium cynomolgi. Furthermore, HDP from P. vinckei (PvHDP) was over-expressed and purified for detailed characterization. The PvHDP is cytosolic, expressed throughout the intra erythrocytic stages and its expression is higher in late trophozoite and schizont stages of parasite. The PvHDP interacts with free heme (KD=89 nM) and efficiently converts heme into hemozoin in a time and concentration dependent manner. Moreover, PvHDP showed activity in acidic pH and over a broad range of temperature. Histidine modification of PvHDP using DEPC showed reduction in heme binding and hemozoin formation, thus emphasizing the importance of histidine residues in heme binding and subsequent hemozoin production. Furthermore, applicability of PvHDP to screen anti-plasmodial agents (targeting heme to hemozoin conversion) was also determined using chloroquine, and mefloquine as reference antimalarials. Results showed that these drugs inhibit heme polymerization effectively in a concentration dependent manner. In conclusion, our study identified and biochemically characterized HDP from rodent malaria parasite P. vinckei and this will help to develop a high throughput assay to evaluate new antimalarials targeting hemozoin pathway. Copyright © 2015 Elsevier B.V. All

  9. Malaria

    Science.gov (United States)

    Quartan malaria; Falciparum malaria; Biduoterian fever; Blackwater fever; Tertian malaria; Plasmodium ... now only suggested for use in areas where Plasmodium vivax , P. ... is becoming increasingly resistant to anti-malarial medications ...

  10. Collapsing Focal Segmental Glomerulosclerosis in a Patient with Acute Malaria

    Directory of Open Access Journals (Sweden)

    Najamus Sehar

    2015-01-01

    seen in association with HIV infection. Rare data is available about the association between collapsing FSGS and malaria. Case Description. A 72-year-old African male patient presented to the hospital for generalized body aches, fatigue, fever, and night sweats for three days. He had history of recent travel to Ghana. Patient looked in acute distress and was shivering. Laboratory tests showed elevated serum creatinine (Cr of 2.09 mg/dL (baseline was 1.5 mg/dL in 2012. Hospital course was significant for rapid elevation of Cr to 9.5 mg/dL and proteinuria of 7.9 grams. Autoimmune studies resulted negative. Blood smear resulted positive for Plasmodium falciparum and patient was treated with Artemether/Lumefantrine. Patient’s fever and pain improved, but kidney function continued to deteriorate and he became oliguric. On day seven, he was started on Hemodialysis. Tests for different causes of glomerular pathology were also negative. He underwent left kidney biopsy which resulted in findings consistent with severe collapsing glomerulopathy. Discussion. This case illustrates a biopsy proven collapsing FSGS likely secondary to malarial infection requiring renal replacement therapy. Literature review revealed only few case reports that suggested the possible association of malaria with secondary form of FSGS.

  11. The antibody response to well-defined malaria antigens after acute malaria in individuals living under continuous malaria transmission

    DEFF Research Database (Denmark)

    Petersen, E; Høgh, B; Dziegiel, M

    1992-01-01

    , and a synthetic peptide (EENV)6 representing the C-terminal repeats from Pf155/RESA, were investigated longitudinally in 13 children and 7 adults living under conditions of continuous, intense malaria transmission. Some subjects did not recognize the antigens after malaria infection, and in subjects recognizing...... elicited by natural malaria infection in previously primed donors....

  12. Description of Anopheles gabonensis, a new species potentially involved in rodent malaria transmission in Gabon, Central Africa.

    Science.gov (United States)

    Rahola, Nil; Makanga, Boris; Yangari, Patrick; Jiolle, Davy; Fontenille, Didier; Renaud, François; Ollomo, Benjamin; Ayala, Diego; Prugnolle, Franck; Paupy, Christophe

    2014-12-01

    The genus Anopheles includes mosquito vectors of human malaria and arboviruses. In sub-Saharan Africa, the anopheline fauna is rich of nearly 150 species, few of which are anthropophilic and capable of transmitting pathogens to humans. Some of the remaining species are found in forests far from human environments and are vectors of wildlife pathogens. The diversity and the biology of these species have yet to be fully described. As a contribution to furthering knowledge of sylvan Anophelinae, using morphological and molecular tools we describe a new Anopheles species collected in Gabon (Central Africa), which we have named Anopheles gabonensis n. sp. We also molecularly screened this species to detect infections by Plasmodium parasites. The results showed the species to have been infected by Plasmodium vinckei, a rodent parasite. We discuss the role of An. gabonensis n. sp. in the transmission of P. vinckei in the rainforest areas of Central Africa and its potential to transfer pathogens to humans.

  13. Malaria

    Science.gov (United States)

    ... and can even be fatal. SymptomsWhat are the symptoms of malaria?The symptoms of malaria include:High fever (can often be 104° F ... give someone else malaria?If I do get malaria, should I travel while I have symptoms? Other organizationsInternational Society of Travel MedicineCenters for Disease ...

  14. Evidence for pyronaridine as a highly effective partner drug for treatment of artemisinin-resistant malaria in a rodent model.

    Science.gov (United States)

    Henrich, Philipp P; O'Brien, Connor; Sáenz, Fabián E; Cremers, Serge; Kyle, Dennis E; Fidock, David A

    2014-01-01

    The increasing prevalence in Southeast Asia of Plasmodium falciparum infections with delayed parasite clearance rates, following treatment of malaria patients with the artemisinin derivative artesunate, highlights an urgent need to identify which of the currently available artemisinin-based combination therapies (ACTs) are most suitable to treat populations with emerging artemisinin resistance. Here, we demonstrate that the rodent Plasmodium berghei SANA strain has acquired artemisinin resistance following drug pressure, as defined by reduced parasite clearance and early recrudescence following daily exposure to high doses of artesunate or the active metabolite dihydroartemisinin. Using the SANA strain and the parental drug-sensitive N strain, we have interrogated the antimalarial activity of five ACTs, namely, artemether-lumefantrine, artesunate-amodiaquine, artesunate-mefloquine, dihydroartemisinin-piperaquine, and the newest combination artesunate-pyronaridine. By monitoring parasitemia and outcome for 30 days following initiation of treatment, we found that infections with artemisinin-resistant P. berghei SANA parasites can be successfully treated with artesunate-pyronaridine used at doses that are curative for the parental drug-sensitive N strain. No other partner drug combination was as effective in resolving SANA infections. Of the five partner drugs tested, pyronaridine was also the most effective at suppressing the recrudescence of SANA parasites. These data support the potential benefit of implementing ACTs with pyronaridine in regions affected by artemisinin-resistant malaria.

  15. Malaria.

    Science.gov (United States)

    Dupasquier, Isabelle

    1989-01-01

    Malaria, the greatest pandemia in the world, claims an estimated one million lives each year in Africa alone. While it may still be said that for the most part malaria is found in what is known as the world's poverty belt, cases are now frequently diagnosed in western countries. Due to resistant strains of malaria which have developed because of…

  16. Malaria.

    Science.gov (United States)

    Dupasquier, Isabelle

    1989-01-01

    Malaria, the greatest pandemia in the world, claims an estimated one million lives each year in Africa alone. While it may still be said that for the most part malaria is found in what is known as the world's poverty belt, cases are now frequently diagnosed in western countries. Due to resistant strains of malaria which have developed because of…

  17. Oral vaccination of mice against rodent malaria with recombinant expressing MSP-119

    Institute of Scientific and Technical Information of China (English)

    Zhi-Hong Zhang; Pei-Hong Jiang; Ning-Jun Li; Mi Shi; Weida Huang

    2005-01-01

    AIM: To construct the recombinant Lactococcus lactis as oral delivery vaccination against malaria.METHODS: The C-terminal 19-ku fragments of MSP1(MSP-119) of Plasmodium yoelii265-BY was expressed in L. lactis and the recombinant L. lactis was administered orally to BALB/c and C57BL/6 mice. After seven interval vaccinations within 4 wk, the mice were challenged with P.yoelii 265-BY parasites of erythrocytic stage. The protective efficacy of recombinant L.lactiswas evaluated.RESULTS: The peak parasitemias in average for the experiment groups of BALB/c and C57BL/6 mice were 0.8±0.4% and 20.8±26.5%, respectively, and those of their control groups were 12.0±0.8% and 60.8±9.6%, respectively. None of the BALB/c mice in both experimental group and control group died during the experiment.However, all the C57BL/6 mice in the control group died within 23 d and all the vaccinated mice survived well.CONCLUSION: The results imply the potential of recombinant L.lactis as oral delivery vaccination against malaria.

  18. A nonadjuvanted polypeptide nanoparticle vaccine confers long-lasting protection against rodent malaria.

    Science.gov (United States)

    Kaba, Stephen A; Brando, Clara; Guo, Qin; Mittelholzer, Christian; Raman, Senthilkumar; Tropel, David; Aebi, Ueli; Burkhard, Peter; Lanar, David E

    2009-12-01

    We have designed and produced a prototypic malaria vaccine based on a highly versatile self-assembling polypeptide nanoparticle (SAPN) platform that can repetitively display antigenic epitopes. We used this platform to display a tandem repeat of the B cell immunodominant repeat epitope (DPPPPNPN)(2)D of the malaria parasite Plasmodium berghei circumsporozoite protein. Administered in saline, without the need for a heterologous adjuvant, the SAPN construct P4c-Mal conferred a long-lived, protective immune response to mice with a broad range of genetically distinct immune backgrounds including the H-2(b), H-2(d), and H-2(k) alleles. Immunized mice produced a CD4(+) T cell-dependent, high-titer, long-lasting, high-avidity Ab response against the B cell epitope. Mice were protected against an initial challenge of parasites up to 6 mo after the last immunization or for up to 15 mo against a second challenge after an initial challenge of parasites had successfully been cleared. Furthermore, we demonstrate that the SAPN platform not only functions to deliver an ordered repetitive array of B cell peptide epitopes but operates as a classical immunological carrier to provide cognate help to the P4c-Mal-specific B cells.

  19. Etiology of Acute, Non-Malaria, Febrile Illnesses in Jayapura, Northeastern Papua, Indonesia

    Science.gov (United States)

    2012-01-01

    the towns of Abepura (population = 46,000) and Sentani (population = 30,000), and the surrounding countryside, including the palm oil ...Hygiene INTRODUCTION Throughout Papua, Indonesia , malaria has been an impor- tant disease for many years, accounting for 16% of all hospital...Ministry of Health, the Etiology of Acute, Non-Malaria, Febrile Illnesses in Jayapura, Northeastern Papua, Indonesia Narain H. Punjabi ,* Walter R. J

  20. Acute Malaria Induces PD1+CTLA4+ Effector T Cells with Cell-Extrinsic Suppressor Function.

    Directory of Open Access Journals (Sweden)

    Maria Sophia Mackroth

    2016-11-01

    Full Text Available In acute Plasmodium falciparum (P. falciparum malaria, the pro- and anti-inflammatory immune pathways must be delicately balanced so that the parasitemia is controlled without inducing immunopathology. An important mechanism to fine-tune T cell responses in the periphery is the induction of coinhibitory receptors such as CTLA4 and PD1. However, their role in acute infections such as P. falciparum malaria remains poorly understood. To test whether coinhibitory receptors modulate CD4+ T cell functions in malaria, blood samples were obtained from patients with acute P. falciparum malaria treated in Germany. Flow cytometric analysis showed a more frequent expression of CTLA4 and PD1 on CD4+ T cells of malaria patients than of healthy control subjects. In vitro stimulation with P. falciparum-infected red blood cells revealed a distinct population of PD1+CTLA4+CD4+ T cells that simultaneously produced IFNγ and IL10. This antigen-specific cytokine production was enhanced by blocking PD1/PDL1 and CTLA4. PD1+CTLA4+CD4+ T cells were further isolated based on surface expression of PD1 and their inhibitory function investigated in-vitro. Isolated PD1+CTLA4+CD4+ T cells suppressed the proliferation of the total CD4+ population in response to anti-CD3/28 and plasmodial antigens in a cell-extrinsic manner. The response to other specific antigens was not suppressed. Thus, acute P. falciparum malaria induces P. falciparum-specific PD1+CTLA4+CD4+ Teffector cells that coproduce IFNγ and IL10, and inhibit other CD4+ T cells. Transient induction of regulatory Teffector cells may be an important mechanism that controls T cell responses and might prevent severe inflammation in patients with malaria and potentially other acute infections.

  1. A comparative study of regression of jaundice in patients of malaria and acute viral hepatitis

    Directory of Open Access Journals (Sweden)

    D.K. Kochar, K. Kaswan, S.K. Kochar, P. Sirohi, M. Pala, A. Kochar , R.P. Agrawal , A. Das

    2006-09-01

    Full Text Available Background & objectives: Jaundice is one of the common manifestations of severe malaria in adults.The purpose of this study is to compare the pattern of clinical and biochemical parameters such asserum bilirubin and liver enzyme levels in patients of malaria with jaundice and acute viral hepatitis.Methodology: The present study was conducted on 34 patients of malaria with jaundice and 15patients of acute viral hepatitis. Estimation of serum bilirubin, aspartate amino transferase (AST,alanine amino transferase (ALT and alkaline phosphatase was done daily using standard proceduresin malaria patients and weekly in acute viral hepatitis patients.Results: Mean level of serum bilirubin on first day in malaria and acute viral hepatitis patients was7.07 ± 3.94 and 10.38 ± 7.87 mg%, whereas on Day 8 it was 1.19 ± 1.43 and 7.88 ± 7.02 mg%respectively. Mean level of AST on Day 1 in malaria and acute viral hepatitis patients was 158.47 ±120.35 and 1418.6 ± 834.11 IU/L, whereas on Day 8 it was 41 ± 28.33 and 775.3 ± 399.01IU/L respectively. Mean level of ALT on Day 1 in malaria and acute viral hepatitis patients was220.14 ± 145.61 and 1666.67 ± 1112.77 IU/L, whereas on Day 8 it was 50.85 ± 37.31 and 823.8 ±475.06 IU/L respectively. Mean level of serum alkaline phosphatase on Day 1 in malaria and acuteviral hepatitis patients was 394.74 ± 267.78 and 513.4 ± 324.7 IU/L, whereas on Day 8 it was84.76 ± 68.50 and 369.27 ± 207.75 IU/L respectively.Interpretation & conclusion: We observed that resolution of jaundice in malaria took 1–2 weeks incontrast 6 to 8 weeks in viral hepatitis. This difference in duration was statistically significant. Thus,jaundice not resolving in 1–2 weeks time in a patient of malaria requires serious consideration forpresence of other concomitant diseases including viral hepatitis.

  2. Targeting Neutrophils to Prevent Malaria-Associated Acute Lung Injury/Acute Respiratory Distress Syndrome in Mice

    Science.gov (United States)

    Soeiro-Pereira, Paulo V.; Gomes, Eliane; Neto, Antonio Condino; D' Império Lima, Maria R.; Alvarez, José M.; Portugal, Silvia; Epiphanio, Sabrina

    2016-01-01

    Malaria remains one of the greatest burdens to global health, causing nearly 500,000 deaths in 2014. When manifesting in the lungs, severe malaria causes acute lung injury/acute respiratory distress syndrome (ALI/ARDS). We have previously shown that a proportion of DBA/2 mice infected with Plasmodium berghei ANKA (PbA) develop ALI/ARDS and that these mice recapitulate various aspects of the human syndrome, such as pulmonary edema, hemorrhaging, pleural effusion and hypoxemia. Herein, we investigated the role of neutrophils in the pathogenesis of malaria-associated ALI/ARDS. Mice developing ALI/ARDS showed greater neutrophil accumulation in the lungs compared with mice that did not develop pulmonary complications. In addition, mice with ALI/ARDS produced more neutrophil-attracting chemokines, myeloperoxidase and reactive oxygen species. We also observed that the parasites Plasmodium falciparum and PbA induced the formation of neutrophil extracellular traps (NETs) ex vivo, which were associated with inflammation and tissue injury. The depletion of neutrophils, treatment with AMD3100 (a CXCR4 antagonist), Pulmozyme (human recombinant DNase) or Sivelestat (inhibitor of neutrophil elastase) decreased the development of malaria-associated ALI/ARDS and significantly increased mouse survival. This study implicates neutrophils and NETs in the genesis of experimentally induced malaria-associated ALI/ARDS and proposes a new therapeutic approach to improve the prognosis of severe malaria. PMID:27926944

  3. Transient depletion of T cells with high LFA-1 expression from peripheral circulation during acute Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Hviid, L; Theander, T G; Abdulhadi, N H

    1991-01-01

    Acute P. falciparum malaria is associated with loss of in vitro T cell responsiveness to antigenic stimulation, and with high plasma levels of soluble interleukin 2 receptor (IL 2R). In the present study peripheral T cells from acute P. falciparum malaria patients from a malaria-endemic area......-bound IL 2R (CD25) and ICAM-1 (CD54) did not reveal in vivo activated T cells in the peripheral blood of the patients. Taken together, these data suggest that circulating T cells recognizing parasite antigens are temporarily withdrawn from peripheral circulation during P. falciparum malaria....

  4. Efficient monitoring of the blood-stage infection in a malaria rodent model by the rotating-crystal magneto-optical method

    Science.gov (United States)

    Orbán, Ágnes; Rebelo, Maria; Molnár, Petra; Albuquerque, Inês S.; Butykai, Adam; Kézsmárki, István

    2016-03-01

    Intense research efforts have been focused on the improvement of the efficiency and sensitivity of malaria diagnostics, especially in resource-limited settings for the detection of asymptomatic infections. Our recently developed magneto-optical (MO) method allows the accurate quantification of malaria pigment crystals (hemozoin) in blood by their magnetically induced rotation. First evaluations of the method using β-hematin crystals and in vitro P. falciparum cultures implied its potential for high-sensitivity malaria diagnosis. To further investigate this potential, here we study the performance of the method in monitoring the in vivo onset and progression of the blood-stage infection in a rodent malaria model. Our results show that the MO method can detect the first generation of intraerythrocytic P. berghei parasites 66-76 hours after sporozoite injection, demonstrating similar sensitivity to Giesma-stained light microscopy and exceeding that of flow cytometric techniques. Magneto-optical measurements performed during and after the treatment of P. berghei infections revealed that both the follow up under treatment and the detection of later reinfections are feasible with this new technique. The present study demonstrates that the MO method - besides being label and reagent-free, automated and rapid - has a high in vivo sensitivity and is ready for in-field evaluation.

  5. Blood monocyte oxidative burst activity in acute P. falciparum malaria

    DEFF Research Database (Denmark)

    Nielsen, H; Theander, T G

    1989-01-01

    The release of superoxide anion from blood monocytes was studied in eight patients with acute primary attack P. falciparum malaria. Before treatment a significant enhancement of the oxidative burst prevailed, which contrasts with previous findings of a depressed monocyte chemotactic responsiveness....... During treatment and after clinical recovery the activity of superoxide anion release normalized in all patients....

  6. Laboratory prediction of the requirement for renal replacement in acute falciparum malaria

    NARCIS (Netherlands)

    Hanson, J.; Hasan, M.M.U.; Royakkers, A.A.; Alam, S.; Charunwatthana, P.; Maude, R.J.; Douthwaite, S.T.; Yunus, E.B.; Mantha, M.L.; Schultz, M.J.; Faiz, M.A.; White, N.J.; Day, N.P.; Dondorp, A.M.

    2011-01-01

    Acute renal failure is a common complication of severe malaria in adults, and without renal replacement therapy (RRT), it carries a poor prognosis. Even when RRT is available, delaying its initiation may increase mortality. Earlier identification of patients who will need RRT may improve outcomes. P

  7. Acute Renal Failure in Patients with Severe Falciparum Malaria: Using the WHO 2006 and RIFLE Criteria

    Directory of Open Access Journals (Sweden)

    Vipa Thanachartwet

    2013-01-01

    Full Text Available There are limited data on the application of the RIFLE criteria among patients with severe malaria. This retrospective study was conducted by reviewing 257 medical records of adult hospitalized patients with severe falciparum malaria at the Mae Sot General Hospital, Tak province in the northern part of Thailand. The aims of this study were to determine the incidence of acute renal failure (ARF in patients with severe falciparum malaria and its association with RRT as well as in-hospital mortality. Using the WHO 2006 criteria, ARF was the second most common complication with incidence of 44.7% (115 patients. The requirement for RRT was 45.2% (52 patients and the in-hospital mortality was 31.9% (36 patients. Using the RIFLE criteria, 73.9% (190 patients had acute kidney injury (AKI. The requirement for RRT was 11.6% (5 patients in patients with RIFLE-I and 44.9% (48 patients in patients with RIFLE-F. The in-hospital mortality gradually increased with the severity of AKI. The requirement for RRT (P<0.05 and the in-hospital mortality (P<0.05 were significantly higher in ARF patients with severe falciparum malaria using both criteria. In conclusion, the RIFLE criteria could be used for diagnosing AKI and predicting outcomes in patients with severe malaria similar to the WHO 2006 criteria.

  8. Novel Zn2+ Modulated GPR39 Receptor Agonists Do Not Drive Acute Insulin Secretion in Rodents.

    Directory of Open Access Journals (Sweden)

    Ola Fjellström

    Full Text Available Type 2 diabetes (T2D occurs when there is insufficient insulin release to control blood glucose, due to insulin resistance and impaired β-cell function. The GPR39 receptor is expressed in metabolic tissues including pancreatic β-cells and has been proposed as a T2D target. Specifically, GPR39 agonists might improve β-cell function leading to more adequate and sustained insulin release and glucose control. The present study aimed to test the hypothesis that GPR39 agonism would improve glucose stimulated insulin secretion in vivo. A high throughput screen, followed by a medicinal chemistry program, identified three novel potent Zn2+ modulated GPR39 agonists. These agonists were evaluated in acute rodent glucose tolerance tests. The results showed a lack of glucose lowering and insulinotropic effects not only in lean mice, but also in diet-induced obese (DIO mice and Zucker fatty rats. It is concluded that Zn2+ modulated GPR39 agonists do not acutely stimulate insulin release in rodents.

  9. Acute kidney injury in a shepherd with severe malaria: a case report

    Directory of Open Access Journals (Sweden)

    Boushab BM

    2016-10-01

    Full Text Available Boushab Mohamed Boushab,1 Fatim-Zahra Fall-Malick,2 Mamoudou Savadogo,3 Leonardo Kishi Basco,4 1Department of Internal Medicine, Aïoun Regional Hospital, Hodh El Gharbi, Mauritania; 2National Institute of Hepatology-Virology in Nouakchott, School of Medicine, Nouakchott, Mauritania; 3Department of Infectious Diseases, University Teaching Hospital Yalgado Ouédrago, Ouagadougou, Burkina Faso; 4Research Unit of Infectious and Tropical Diseases, Institut de Recherche pour le Développement (Research Institute for Development, Aix-Marseille University, Marseille, France Abstract: Malaria is one of the main reasons for outpatient consultation and hospitalization in Mauritania. Although four Plasmodium species, ie, Plasmodium (P. falciparum, P. vivax, P. malariae, and P. ovale, cause malaria in Mauritania, recent data on their frequency is ­lacking. Since infections with P. falciparum generally result in serious disease, their identification is important. We report a case of oliguric renal injury associated with malaria in a 65-year-old shepherd. Clinical manifestations included anemia, oliguria, and elevated creatinine and urea. The rapid diagnostic test for malaria and microscopic examination of blood smears were positive for P. falciparum. On the basis of this, the patient was diagnosed as having acute kidney injury as a complication of severe malaria. The patient was treated for malaria with intravenous quinine for 4 days, followed by 3 days of oral treatment. Volume expansion, antipyretic treatment, and diuretics were administered. He also had two rounds of dialysis after which he partially recovered renal function. This outcome is not always the rule. Prognosis depends much on early diagnosis and appropriate supportive treatment. Keywords: malaria, oliguric kidney injury, shepherd, quinine, dialysis

  10. Vß profiles in African children with acute cerebral or uncomplicated malaria: very focused changes among a remarkable global stability

    DEFF Research Database (Denmark)

    Loizon, Séverine; Boeuf, Philippe; Tetteh, John K A

    2007-01-01

    T cells are thought to play a critical role in cerebral malaria pathogenesis. However, available evidences are restricted to rodent models in which V beta specific T cell expansion has been associated with neurological syndrome suggesting involvement of superantigens or dominant antigens. Using f...

  11. Oral clindamycin in the treatment of acute uncomplicated falciparum malaria.

    Science.gov (United States)

    Salazar, N P; Saniel, M C; Estoque, M H; Talao, F A; Bustos, D G; Palogan, L P; Gabriel, A I

    1990-09-01

    Clinical trials on oral clindamycin as an antimalarial in hospitalized patients and residents of endemic communities were conducted in the Philippines between May 1984 and December 1985. Seven and 9 qualified subjects in hospital were treated with 300 mg (regimen A) and 600 mg (regimen B) respectively, twice daily for 5 days. Eighteen patients seen at a rural health unit were given the lower dosage. On the basis of the 28-day extended in vivo test of WHO, P. falciparum in all but one patient showed susceptibility to the drug as a blood schizontocide hence, the clinical cure of malaria. Side effects were few and self-limiting. Ten other patients on regimen A were cured within the 7- and/or 28-day extended test period. Clindamycin per se is currently one of the few alternatives in the treatment of clinically moderate drug-resistant malaria.

  12. Malaria.

    Science.gov (United States)

    Heck, J E

    1991-03-01

    Human malaria is caused by four species of the genus plasmodium. The sexual stage of the parasite occurs in the mosquito and asexual reproduction occurs in man. Symptoms of fever, chills, headache, and myalgia result from the invasion and rupture of erythrocytes. Merozoites are released from erythrocytes and invade other cells, thus propagating the infection. The most vulnerable hosts are nonimmune travelers, young children living in the tropics, and pregnant women. P. falciparum causes the most severe infections because it infects RBCs of all ages and has the propensity to develop resistance to antimalarials. Rapid diagnosis can be made with a malarial smear, and treatment should be initiated promptly. In some regions (Mexico, Central America except Panama, and North Africa) chloroquine phosphate is effective therapy. In subsaharan Africa, South America, and Southeast Asia, chloroquine resistance has become widespread, and other antimalarials are necessary. The primary care physician should have a high index of suspicion for malaria in the traveler returning from the tropics. Malaria should also be suspected in the febrile transfusion recipient and newborns of mothers with malaria.

  13. Temporal association of acute hepatitis A and Plasmodium falciparum malaria in children.

    Directory of Open Access Journals (Sweden)

    Peter Klein Klouwenberg

    Full Text Available BACKGROUND: In sub-Saharan Africa, Plasmodium falciparum and hepatitis A (HAV infections are common, especially in children. Co-infections with these two pathogens may therefore occur, but it is unknown if temporal clustering exists. MATERIALS AND METHODS: We studied the pattern of co-infection of P. falciparum malaria and acute HAV in Kenyan children under the age of 5 years in a cohort of children presenting with uncomplicated P. falciparum malaria. HAV status was determined during a 3-month follow-up period. DISCUSSION: Among 222 cases of uncomplicated malaria, 10 patients were anti-HAV IgM positive. The incidence of HAV infections during P. falciparum malaria was 1.7 (95% CI 0.81-3.1 infections/person-year while the cumulative incidence of HAV over the 3-month follow-up period was 0.27 (95% CI 0.14-0.50 infections/person-year. Children with or without HAV co-infections had similar mean P. falciparum asexual parasite densities at presentation (31,000/µL vs. 34,000/µL, respectively, largely exceeding the pyrogenic threshold of 2,500 parasites/µL in this population and minimizing risk of over-diagnosis of malaria as an explanation. CONCLUSION: The observed temporal association between acute HAV and P. falciparum malaria suggests that co-infections of these two hepatotrophic human pathogens may result from changes in host susceptibility. Testing this hypothesis will require larger prospective studies.

  14. Acute respiratory distress syndrome due to vivax malaria: case report and literature review

    Directory of Open Access Journals (Sweden)

    André V. Lomar

    2005-10-01

    Full Text Available Severe pulmonary involvement in malaria has been frequently reported in cases of Plasmodium falciparum infection, but rarely in vivax malaria. Among the 11 previous cases of vivax-related severe respiratory involvement described in the literature, all except one developed it after the beginning of anti-malarial treatment; these appear to correspond to an exacerbation of the inflammatory response. We report the case of a 43-year-old Brazilian woman living in a malaria-endemic area, who presented acute respiratory distress syndrome (ARDS caused by P. vivax before starting anti-malarial treatment. The diagnosis was made based on microscopic methods. A negative rapid immunochromatographic assay, based on the detection of Histidine Rich Protein-2 (HRP-2 of P. falciparum, indicated that falciparum malaria was unlikely. After specific anti-plasmodial therapy and intensive supportive care, the patient was discharged from the hospital. We conclude that vivax malaria-associated ARDS can develop before anti-malarial therapy.

  15. Frutalin reduces acute and neuropathic nociceptive behaviours in rodent models of orofacial pain.

    Science.gov (United States)

    Damasceno, Marina B M V; de Melo Júnior, José de Maria A; Santos, Sacha Aubrey A R; Melo, Luana T M; Leite, Laura Hévila I; Vieira-Neto, Antonio E; Moreira, Renato de A; Monteiro-Moreira, Ana Cristina de O; Campos, Adriana R

    2016-08-25

    Orofacial pain is a highly prevalent clinical condition, yet difficult to control effectively with available drugs. Much attention is currently focused on the anti-inflammatory and antinociceptive properties of lectins. The purpose of this study was to evaluate the antinociceptive effect of frutalin (FTL) using rodent models of inflammatory and neuropathic orofacial pain. Acute pain was induced by formalin, glutamate or capsaicin (orofacial model) and hypertonic saline (corneal model). In one experiment, animals were pretreated with l-NAME and naloxone to investigate the mechanism of antinociception. The involvement of the lectin domain in the antinociceptive effect of FTL was verified by allowing the lectin to bind to its specific ligand. In another experiment, animals pretreated with FTL or saline were submitted to the temporomandibular joint formalin test. In yet another, animals were submitted to infraorbital nerve transection to induce chronic pain, followed by induction of thermal hypersensitivity using acetone. Motor activity was evaluated with the rotarod test. A molecular docking was performed using the TRPV1 channel. Pretreatment with FTL significantly reduced nociceptive behaviour associated with acute and neuropathic pain, especially at 0.5 mg/kg. Antinociception was effectively inhibited by l-NAME and d-galactose. In line with in vivo experiments, docking studies indicated that FTL may interact with TRPV1. Our results confirm the potential pharmacological relevance of FTL as an inhibitor of orofacial nociception in acute and chronic pain mediated by TRPA1, TRPV1 and TRPM8 receptor.

  16. Chemotherapy of Rodent Malaria.

    Science.gov (United States)

    1981-09-01

    Route of administration :sc FORMULATION: Tween 80 /H2 0 Strain Daily dose No. of No. of Mean control Treated PR% X i0C mg/kg DO - D+3 Mice...PARASITE (SUB) SPECIES ........................... FORMULATION Tween 80 /H 0 Route of administration : po 2 Strain Daily dose No. of No. of...Route of administration SCFORMULATION Tween 80 /H20 Daily dose No. of No. of Mean control Treated PR% Strain mg/kg DO - D+3 Mice experiment parasite

  17. Chemotherapy of Rodent Malaria.

    Science.gov (United States)

    1985-07-01

    causal prophylactic test, spiramycin nas a minimum fully effective dose of 30 - 100 mg/kg. Lincomvycin hydrochloride was less active (MFED = > 100 mg/kg...data sheets are appended as Tables132 tnrcugn an i isobolograms are shown in Figures I to 14. 3.5.1 Mefloquine/ spiramycin This combination appears to... mic 2 x pe r imen parasi t ae~Jft- __ __ _ 0 0 t__ _ L 5 3o __ _ _ _ __ __o_ __ _ _ _ _ I. P 1-n e 3 lo _ _ _ _ _-_ __ 1 9 2_ _ _ _ _ N~ S HA Lh

  18. Organotypic tissue culture of adult rodent retina followed by particle-mediated acute gene transfer in vitro.

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    Satoru Moritoh

    Full Text Available BACKGROUND: Organotypic tissue culture of adult rodent retina with an acute gene transfer that enables the efficient introduction of variable transgenes would greatly facilitate studies into retinas of adult rodents as animal models. However, it has been a difficult challenge to culture adult rodent retina. The purpose of this present study was to develop organotypic tissue culture of adult rodent retina followed by particle-mediated acute gene transfer in vitro. METHODOLOGY/PRINCIPAL FINDINGS: We established an interphase organotypic tissue culture for adult rat retinas (>P35 of age which was optimized from that used for adult rabbit retinas. We implemented three optimizations: a greater volume of Ames' medium (>26 mL per retina, a higher speed (constant 55 rpm of agitation by rotary shaker, and a greater concentration (10% of horse serum in the medium. We also successfully applied this method to adult mouse retina (>P35 of age. The organotypic tissue culture allowed us to keep adult rodent retina morphologically and structurally intact for at least 4 days. However, mouse retinas showed less viability after 4-day culture. Electrophysiologically, ganglion cells in cultured rat retina were able to generate action potentials, but exhibited less reliable light responses. After transfection of EGFP plasmids by particle-mediated acute gene transfer, we observed EGFP-expressing retinal ganglion cells as early as 1 day of culture. We also introduced polarized-targeting fusion proteins such as PSD95-GFP and melanopsin-EYFP (hOPN4-EYFP into rat retinal ganglion cells. These fusion proteins were successfully transferred into appropriate locations on individual retinal neurons. CONCLUSIONS/SIGNIFICANCE: This organotypic culture method is largely applicable to rat retinas, but it can be also applied to mouse retinas with a caveat regarding cell viability. This method is quite flexible for use in acute gene transfection in adult rodent retina, replacing

  19. Malaria

    Science.gov (United States)

    2011-06-01

    ceived the Nobel prize in 1902. Grassi et al later proved that anopheline mosquitoes transmit malaria to humans.2 In 2002, researchers sequenced the...Malarial pigment is the end product of hemoglobin diges- tion into a porphyrin conjugated with a protein derived from the globin portion of...location, parasite strain, and the patient’s age, immune status, and treatment.27 Investigating the patient’s travel history may provide clues to the spe

  20. Acute and sub-acute oral toxicity profile of Acorus calamus (Sweet flag) in rodents

    Institute of Scientific and Technical Information of China (English)

    Arunachalam Muthuraman; Nirmal Singh

    2012-01-01

    Objective: To determine the acute and sub-acute oral toxicity profile of the hydroalcoholic extract of Acorus calamus (HAE-AC) in mice and rats respectively. Methods: In acute toxicity study, mice were assessed to any alteration of general behavior and mortality rate within 24 h. Further, in sub-acute toxicity study, rats were used for assessment of mortality, body weight, hematological, biochemical and histopathological changes. Results: Single oral administrations of the HAE-AC 2500-10000 mg/kg induced increase in general behavioral abnormalities in mice. The mortality rate also increased with increasing dosage (median lethal dose; LD50 = 5 070.59 mg/kg). Daily single oral doses of HAE-AC 200, 500 and 1 000 mg/kg were observed to be well tolerated behaviorally after 28 days of dosing and induced no significant changes in body and organs weights of rats. Further, a mild rise in the levels of alanine transaminase (ALT), aspartate transaminase (AST) and histopatholological changes in liver tissue was noted at 1000 mg/kg dose of HAE-AC. Conclusions: Overall, the findings of this study indicate that, HAE-AC is non-toxic and has at high dose, a mild but acceptable toxicity potential.

  1. The plasma concentration of the B cell activating factor is increased in children with acute malaria.

    Science.gov (United States)

    Nduati, Eunice; Gwela, Agnes; Karanja, Henry; Mugyenyi, Cleopatra; Langhorne, Jean; Marsh, Kevin; Urban, Britta C

    2011-09-15

    Malaria-specific antibody responses in children often appear to be short-lived but the mechanisms underlying this phenomenon are not well understood. In this study, we investigated the relationship between the B-cell activating factor (BAFF) and its receptors expressed on B cells with antibody responses during and after acute malaria in children. Our results demonstrate that BAFF plasma levels increased during acute malarial disease and reflected disease severity. The expression profiles for BAFF receptors on B cells agreed with rapid activation and differentiation of a proportion of B cells to plasma cells. However, BAFF receptor (BAFF-R) expression was reduced on all peripheral blood B cells during acute infection, but those children with the highest level of BAFF-R expression on B cells maintained schizont-specific immunoglobin G (IgG) over a period of 4 months, indicating that dysregulation of BAFF-R expression on B cells may contribute to short-lived antibody responses to malarial antigens in children. In summary, this study suggests a potential role for BAFF during malaria disease, both as a marker for disease severity and in shaping the differentiation pattern of antigen-specific B cells.

  2. Effect of acute Plasmodium falciparum malaria on reactivation and shedding of the eight human herpes viruses.

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    Arnaud Chêne

    Full Text Available Human herpes viruses (HHVs are widely distributed pathogens. In immuno-competent individuals their clinical outcomes are generally benign but in immuno-compromised hosts, primary infection or extensive viral reactivation can lead to critical diseases. Plasmodium falciparum malaria profoundly affects the host immune system. In this retrospective study, we evaluated the direct effect of acute P. falciparum infection on reactivation and shedding of all known human herpes viruses (HSV-1, HSV-2, VZV, EBV, CMV, HHV-6, HHV-7, HHV-8. We monitored their presence by real time PCR in plasma and saliva of Ugandan children with malaria at the day of admission to the hospital (day-0 and 14 days later (after treatment, or in children with mild infections unrelated to malaria. For each child screened in this study, at least one type of HHV was detected in the saliva. HHV-7 and HHV-6 were detected in more than 70% of the samples and CMV in approximately half. HSV-1, HSV-2, VZV and HHV-8 were detected at lower frequency. During salivary shedding the highest mean viral load was observed for HSV-1 followed by EBV, HHV-7, HHV-6, CMV and HHV-8. After anti-malarial treatment the salivary HSV-1 levels were profoundly diminished or totally cleared. Similarly, four children with malaria had high levels of circulating EBV at day-0, levels that were cleared after anti-malarial treatment confirming the association between P. falciparum infection and EBV reactivation. This study shows that acute P. falciparum infection can contribute to EBV reactivation in the blood and HSV-1 reactivation in the oral cavity. Taken together our results call for further studies investigating the potential clinical implications of HHVs reactivation in children suffering from malaria.

  3. Successful treatment of malaria tropica with acute renal failure and cerebral involvement by plasmapheresis and hemodialysis.

    Science.gov (United States)

    Stuby, U; Kaiser, W; Biesenbach, G; Zazgornik, J

    1988-01-01

    A non-immune, 31-year-old woman developed an acute infection with Plasmodium falciparum after travelling to Kenia. The parasites proved resistant to chloroquine and sulfadoxine/pyrimethamine. The course of the disease was complicated by acute renal failure, hepatocellular damage, disorders of blood coagulation, thrombocytopenia, hemolysis and cerebral involvement. Despite a very high level of parasitemia (50% parasitized erythrocytes) a rapid clinical improvement was achieved by plasmapheresis and hemodialysis. Our experience shows that plasmapheresis and hemodialysis are excellent additive methods which rapidly improve clinical symptoms and may reduce morbidity and mortality in severe malaria tropica.

  4. Nuclear factor kappa B in urine sediment: a useful indicator to detect acute kidney injury in Plasmodium falciparum malaria.

    Science.gov (United States)

    Punsawad, Chuchard; Viriyavejakul, Parnpen

    2014-03-07

    Acute kidney injury (AKI) is one of the major complications of Plasmodium falciparum malaria, especially among non-immune adults. It has recently been revealed that activation of transcription factor nuclear factor kappa B (NF-κB) induces pro-inflammatory gene expression involved in the development of progressive renal inflammatory diseases. The aim of this study was to determine whether urinary sediment NF-κB p65 can act as a biomarker for AKI in patients with P. falciparum malaria. Urinary sediments from malaria patients, including Plasmodium vivax malaria, uncomplicated P. falciparum malaria, complicated P. falciparum malaria without AKI (serum creatinine-Cr falciparum malaria with AKI (Cr ≥3 mg/dl) were used to determine NF-κB p65 level by sandwich enzyme-linked immunosorbent assay (ELISA). Urinary sediments obtained from healthy controls were used as a normal baseline. Correlations between levels of urinary sediment NF-κB p65 and pertinent clinical data were analysed. Urinary sediment NF-κB p65 levels were significantly increased on the day of admission (day 0) and on day 7 post-treatment in complicated P. falciparum malaria patients with AKI, compared with those without AKI (p=0.001, p falciparum malaria.

  5. Acute and subacute oral toxicity evaluation of Tephrosia purpurea extract in rodents

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    Talib Hussain

    2012-04-01

    Full Text Available Objective: To evaluate the acute and subacute toxicity of 50% ethanolic extract of Tephrosia purpurea (T. purpurea in rodents. Methods: The acute toxicity test was conducted in Swiss albino mice. The extract of T. purpurea was administrated in single doses of 50, 300 and 2000 mg/ kg and observed for behavioral changes and mortality, if any. In subacute toxicity study, Wistar rats of either sex were administered two doses of T. purpurea i.e., 200 and 400 mg/kg (One-tenth and one-fifth of the maximum tolerated dose, p.o. for 4 weeks. During 28 days of treatment, rats were observed weekly for any change in their body weight, food and water intake. At the end of 28 days, rats were sacrificed for hematological, biochemical and histopathology study. Results: In the acute toxicity study, T. purpurea was found to be well tolerated upto 2 000 mg/kg, produced neither mortality nor changes in behavior in mice. In subacute toxicity study, T. purpurea at dose level of 200 and 400 mg/kg did not produce any significant difference in their body weight, food and water intake when compared to vehicle treated rats. It also showed no significant alteration in hematological and biochemical parameters in experimental groups of rats apart from a decrease in aspartate transaminase, alanine transaminase and alkaline phosphate content at the dose of 400 mg/kg. Histopathological study revealed normal architecture of kidney and liver of T. purpurea treated rats. Conclusions: These results demonstrated that there is a wide margin of safety for the therapeutic use of T. purpurea and further corroborated the traditional use of this extract as an anti hepatocarcinogenic agent

  6. Experimental evolution of resistance to artemisinin combination therapy results in amplification of the mdr1 gene in a rodent malaria parasite.

    Directory of Open Access Journals (Sweden)

    Louise A Rodrigues

    Full Text Available BACKGROUND: Lacking suitable alternatives, the control of malaria increasingly depends upon Artemisinin Combination Treatments (ACT: resistance to these drugs would therefore be disastrous. For ACTs, the biology of resistance to the individual components has been investigated, but experimentally induced resistance to component drugs in combination has not been generated. METHODOLOGY/PRINCIPAL FINDINGS: We have used the rodent malaria parasite Plasmodium chabaudi to select in vivo resistance to the artesunate (ATN+mefloquine (MF version of ACT, through prolonged exposure of parasites to both drugs over many generations. The selection procedure was carried out over twenty-seven consecutive sub-inoculations under increasing ATN+MF doses, after which a genetically stable resistant parasite, AS-ATNMF1, was cloned. AS-ATNMF1 showed increased resistance to ATN+MF treatment and to artesunate or mefloquine administered separately. Investigation of candidate genes revealed an mdr1 duplication in the resistant parasites and increased levels of mdr1 transcripts and protein. There were no point mutations in the atpase6 or ubp1genes. CONCLUSION: Resistance to ACTs may evolve even when the two drugs within the combination are taken simultaneously and amplification of the mdr1 gene may contribute to this phenotype. However, we propose that other gene(s, as yet unidentified, are likely to be involved.

  7. Pyronaridine-Artesunate combination for the treatment of acute uncomplicated Plasmodium falciparum malaria in paediatric patients in Gabon

    OpenAIRE

    Schreier, Annette

    2010-01-01

    Artemisinin-based combination therapies (ACTs) are now the recommended first-line drugs for the treatment of acute uncomplicated Plasmodium falciparum malaria in many endemic regions and the development of novel therapy options, especially for the use in children, is a major aim in malaria research. This Phase II study intended to provide first clinical data about the new combination of pyronaridine and artesunate for the use in paediatric patients. 60 children were assigned to the four s...

  8. Value of Plasmodium falciparum Histidine-Rich Protein 2 Level and Malaria Retinopathy in Distinguishing Cerebral Malaria From Other Acute Encephalopathies in Kenyan Children

    Science.gov (United States)

    Kariuki, Symon M.; Gitau, Evelyn; Gwer, Samson; Karanja, Henry K.; Chengo, Eddie; Kazungu, Michael; Urban, Britta C.; Newton, Charles R. J. C.

    2014-01-01

    Background. The diagnosis of cerebral malaria is problematic in malaria-endemic areas because encephalopathy in patients with parasitemia may have another cause. Abnormal retinal findings are thought to increase the specificity of the diagnosis, and the level of histidine-rich protein 2 (HRP2) may reflect the parasite biomass. Methods. We examined the retina and measured plasma HRP2 levels in children with acute nontraumatic encephalopathy in Kenya. Logistic regression, with HRP2 level as an independent variable and World Health Organization–defined cerebral malaria and/or retinopathy as the outcome, was used to calculate malaria-attributable fractions (MAFs) and retinopathy-attributable fractions (RAFs). Results. Of 270 children, 140 (52%) had peripheral parasitemia, 80 (30%) had malaria retinopathy, and 164 (61%) had an HRP2 level of >0 U/mL. During 2006–2011, the incidence of HRP2 positivity among admitted children declined by 49 cases per 100 000 per year (a 78% reduction). An HRP2 level of >0 U/mL had a MAF of 93% for cerebral malaria, with a MAF of 97% observed for HRP2 levels of ≥10 U/mL (the level of the best combined sensitivity and specificity). HRP2 levels of >0 U/mL had a RAF of 77% for features of retinopathy combined, with the highest RAFs for macular whitening (99%), peripheral whitening (98%), and hemorrhages (90%). Conclusion. HRP2 has a high attributable fraction for features of malarial retinopathy, supporting its use in the diagnosis of cerebral malaria. HRP2 thresholds improve the specificity of the definition. PMID:24041795

  9. Sickle cell trait is associated with controlled levels of haem and mild proinflammatory response during acute malaria infection

    Science.gov (United States)

    Ademolue, T. W.; Amodu, O. K.

    2017-01-01

    Summary The controlled induction of haemoxygenase‐1 (HO‐1), an enzyme that catabolizes haem, has been shown to reduce haem, preventing pathologies associated with haem toxicity. The hemoglobin genotype HbAS confers reduced susceptibility to severe complications of malaria by a mechanism that is not well understood. Using a longitudinal approach, we investigated the effect of baseline concentrations of HO‐1 on the accumulation of haem during acute Plasmodium falciparum malaria in HbAS and HbAA genotypes. Plasma concentrations of haem, HO‐1 and cytokines were quantified in venous blood obtained from children (9 months–5 years of age) during malaria infection, and at convalescence (baseline levels). Parasitaemia was determined during malaria infection. In patients with the HbAA genotype, there was a significant elevation in the plasma concentration of haem (P = 0.002), and a consequent increased induction of HO‐1 (P < 0.001) during falciparum malaria compared with levels at convalescence. Contrary to HbAA, plasma concentration of haem did not change in the HbAS genotypical group (P = 0·110), and the induction of HO‐1 was reduced during malaria compared with levels at convalescence (P = 0·006). Higher plasma levels of haem were observed in HbAS compared with HbAA at convalescence (P = 0·010), but this difference did not affect the levels of HO‐1 within each genotype (P = 0·450). Relatively milder proinflammatory responses were observed in HbAS children during malaria infection compared to HbAA children. Our findings suggest that a mechanism of reduced susceptibility to severe malaria pathologies by the HbAS genotype may involve the control of haem, leading to controlled levels of HO‐1 and milder proinflammatory responses during acute malaria. PMID:28142190

  10. Acute Kidney Injury in Children with Plasmodium falciparum Malaria: Determinants for Mortality.

    Science.gov (United States)

    Prasad, Rajniti; Mishra, Om P

    2016-01-01

    Acute kidney injury (AKI) in P. falciparum malaria infection is an important morbidity in children. The purpose of the present study was done to observe the renal involvement, associated morbidities and outcome. ♦ Out of 156 patients with severe P. falciparum malaria, diagnosed on the basis of compatible clinical presentations and positive malarial parasites in the peripheral blood smear and/or histidine rich protein 2 antigen, 31 had AKI at presentation and were analyzed. ♦ Of 31 (19.9%) patients with AKI, 4 were classified at risk, 11 injury, and 16 failure stage, as per pRIFLE criteria (pediatric version of RIFLE [R = risk, I = injury, F = failure, L = loss E = end-stage kidney disease]). Mean age of children with AKI was 7.7 ± 3.2 years. A significantly higher proportion of patients with AKI had hypoglycemia (41.9%), pulmonary edema (32.2%), and disseminated intravascular coagulation (DIC) (29.0%) compared to those without AKI (18.4%, 4.8%, and 3.2%, respectively). Twelve patients (38.7%) required peritoneal dialysis (PD), 8 (25.8%) died, and all were in failure stage. The non-survivors had significantly higher blood urea (p = 0.005) and serum creatinine levels (p = 0.042), lower glomerular filtration rate (p falciparum malaria is one of the severe systemic complications. Duration of illness and presence of comorbidities adversely affected the outcome. Copyright © 2016 International Society for Peritoneal Dialysis.

  11. The genetic risk of acute seizures in African children with falciparum malaria

    Science.gov (United States)

    Kariuki, Symon M; Rockett, Kirk; Clark, Taane G; Reyburn, Hugh; Agbenyega, Tsiri; Taylor, Terrie E; Birbeck, Gretchen L; Williams, Thomas N; Newton, Charles R J C

    2013-01-01

    Purpose It is unclear why some children with falciparum malaria develop acute seizures and what determines the phenotype of seizures. We sought to determine if polymorphisms of malaria candidate genes are associated with acute seizures. Methods Logistic regression was used to investigate genetic associations with malaria-associated seizures (MAS) and complex MAS (repetitive, prolonged, or focal seizures) in four MalariaGEN African sites, namely: Blantyre, Malawi; Kilifi, Kenya; Kumasi, Ghana; and Muheza, Tanzania. The analysis was repeated for five inheritance models (dominant, heterozygous, recessive, additive, and general) and adjusted for potential confounders and multiple testing. Key Findings Complex phenotypes of seizures constituted 71% of all admissions with MAS across the sites. MAS were strongly associated with cluster of differentiation-ligand-rs3092945 in females in Kilifi (p = 0.00068) and interleukin (IL)-17 receptor E-rs708567 in the pooled analysis across the sites (p = 0.00709). Complex MAS were strongly associated with epidermal growth factor module-containing mucin-like hormone receptor (EMR)1-rs373533 in Kumasi (p = 0.00033), but none in the pooled analysis. Focal MAS were strongly associated with IL-20 receptor A-rs1555498 in Muheza (p = 0.00016), but none in the pooled analysis. Prolonged MAS were strongly associated with complement receptor 1-rs17047660 in Kilifi (p = 0.00121) and glucose-6-phosphate dehydrogenase-rs1050828 in females in the pooled analysis (p = 0.00155). Repetitive MAS were strongly associated with EMR1-rs373533 in Kumasi (p = 0.00003) and cystic fibrosis transmembrane conductance receptor-rs17140229 in the pooled analysis (p = 0.00543). MAS with coma/cerebral malaria were strongly associated with EMR1-rs373533 in Kumasi (p = 0.00019) and IL10-rs3024500 in the pooled analysis across the sites (p = 0.00064). Significance We have identified a number of genetic associations that may explain the risk of seizures in >2,000 cases

  12. Impact of acute malaria on pre-existing antibodies to viral and vaccine antigens in mice and humans.

    Directory of Open Access Journals (Sweden)

    Simran Banga

    Full Text Available Vaccine-induced immunity depends on long-lived plasma cells (LLPCs that maintain antibody levels. A recent mouse study showed that Plasmodium chaubaudi infection reduced pre-existing influenza-specific antibodies--raising concerns that malaria may compromise pre-existing vaccine responses. We extended these findings to P. yoelii infection, observing decreases in antibodies to model antigens in inbred mice and to influenza in outbred mice, associated with LLPC depletion and increased susceptibility to influenza rechallenge. We investigated the implications of these findings in Malian children by measuring vaccine-specific IgG (tetanus, measles, hepatitis B before and after the malaria-free 6-month dry season, 10 days after the first malaria episode of the malaria season, and after the subsequent dry season. On average, vaccine-specific IgG did not decrease following acute malaria. However, in some children malaria was associated with an accelerated decline in vaccine-specific IgG, underscoring the need to further investigate the impact of malaria on pre-existing vaccine-specific antibodies.

  13. Acute and chronic toxicity of the methanolic extract of Ajuga iva in rodents

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    Abdelouahab Diafat

    2016-03-01

    Full Text Available Summary. Ajuga iva, known as “Chendgoura”, is widely used in North African countries in the traditional medicine. However, there is little toxicological informations available regarding its safety following repeated exposure. The present investigation describes the toxicity of a methanolic extract of Ajuga iva. The administration of the Ajuga iva methanolic extract (AIME at 2 –14 g/kg of bodyweight (bwt did not produce mortality or significant changes in the general behavior of mice. However, single intraperitoneal injections of AIME (2–6 g/kg bwt produced a dose-dependent increase in adverse effects in the general behavior and the mortality rate. The LD50 by  intraperitoneal route  was 3.980 g/kg bwt. In chronic toxicological studies in rats, oral administration the AIME with daily doses of 100, 300 and 600 mg/kg bwt, did not cause any significant differences in the general conditions like growth, organ weights, hematological and biochemical parameters or in microscopic appearance of the organs (brain, liver and the kidney. In contrast, a transient rise in platelet counts and a decrease in serum glucose and cholesterol levels were noted. Therefore, the NOAEL for the AIME is 600 mg/kg/day administered orally for 13 weeks. So AI methanolic extract has low toxicity. Industrial relevance. The extract of the plant Ajuga iva can be used as herbal teas or for the treatment of several disease such as diabetes, high cholesterol and increased serum triglycerides. However, information regarding its toxicological properties is not available. In this study, we have shown that the methanolic extract of Ajuga iva has low toxicity in rodent models and may be considered for human use after further studies. Keywords. Ajuga iva; methanolic extract; acute toxicity; sub chronic toxicity

  14. False-positive rapid plasma reagin testing in patients with acute Plasmodium vivax malaria: a case control study.

    Science.gov (United States)

    Maves, Ryan C; Dean, Katherine; Gadea, Nilda; Halsey, Eric S; Graf, Paul C F; Lescano, Andres G

    2014-01-01

    Non-treponemal tests such as the rapid plasma reagin (RPR) assay are mainstays of syphilis diagnosis, but false-positive tests are common. We identified false-positive RPR titers in 8.2% of patients with malaria due to Plasmodium vivax in northern Peru. Similar rates were not detected in patients with other acute febrile illnesses.

  15. Prevalence of malaria among acute febrile patients clinically suspected of having malaria in the Zeway Health Center, Ethiopia.

    Science.gov (United States)

    Feleke, Sendeaw M; Animut, Abebe; Belay, Mulugeta

    2015-01-01

    Malaria diagnosis is a common challenge in developing countries with limited diagnostic services. Common febrile illnesses were assessed in 280 malaria-suspected patients, and each case was subjected to clinical and laboratory examinations for malaria, relapsing fever, typhoid fever, typhus, and brucellosis. Data were entered and analyzed using Epi Info version 3.1 software. Malaria accounted for 17% (CI, 12.6-21.4%) of febrile illnesses. The remaining cases were associated with typhoid fever (18.5%; CI, 13.95-23.05%), typhus (17.8%; CI, 13.32-22.28%), brucellosis (1%; CI, -0.17-2.17%), relapsing fever (2%; CI, 0.36-3.64%), and unknown causes (44%). Approximately 7% of patients had coinfections, and 2% of patients treated as monoinfections. Approximately 1.4% of the nonmalarial patients received antimalarial treatment. The sensitivity and specificity of the CareStart Pf/pan rapid diagnostic tests in comparison with those of microscopy were 100% and 91%, respectively, with positive- and negative-predictive values of 94% and 100%, respectively. Compared with microscopy, the positive-predictive value of each malaria symptom was much lower than that of the symptoms combined: fever, 17%; sweating, 30%; headache, 18%; general body ache, 22%; loss of appetite, 21%. The study findings revealed a high proportion of nonmalarial illnesses were clinically categorized as malaria. Parasite-based diagnosis is recommended for the management of malarial and nonmalarial cases.

  16. Parasite burden and CD36-mediated sequestration are determinants of acute lung injury in an experimental malaria model.

    Directory of Open Access Journals (Sweden)

    Fiona E Lovegrove

    2008-05-01

    Full Text Available Although acute lung injury (ALI is a common complication of severe malaria, little is known about the underlying molecular basis of lung dysfunction. Animal models have provided powerful insights into the pathogenesis of severe malaria syndromes such as cerebral malaria (CM; however, no model of malaria-induced lung injury has been definitively established. This study used bronchoalveolar lavage (BAL, histopathology and gene expression analysis to examine the development of ALI in mice infected with Plasmodium berghei ANKA (PbA. BAL fluid of PbA-infected C57BL/6 mice revealed a significant increase in IgM and total protein prior to the development of CM, indicating disruption of the alveolar-capillary membrane barrier-the physiological hallmark of ALI. In contrast to sepsis-induced ALI, BAL fluid cell counts remained constant with no infiltration of neutrophils. Histopathology showed septal inflammation without cellular transmigration into the alveolar spaces. Microarray analysis of lung tissue from PbA-infected mice identified a significant up-regulation of expressed genes associated with the gene ontology categories of defense and immune response. Severity of malaria-induced ALI varied in a panel of inbred mouse strains, and development of ALI correlated with peripheral parasite burden but not CM susceptibility. Cd36(-/- mice, which have decreased parasite lung sequestration, were relatively protected from ALI. In summary, parasite burden and CD36-mediated sequestration in the lung are primary determinants of ALI in experimental murine malaria. Furthermore, differential susceptibility of mouse strains to malaria-induced ALI and CM suggests that distinct genetic determinants may regulate susceptibility to these two important causes of malaria-associated morbidity and mortality.

  17. A case of Plasmodium vivax malaria with spontaneous subarachnoid hemorrhage and acute renal failure, severe thrombocytopenia, with anemia

    Directory of Open Access Journals (Sweden)

    Govind S Shiddapur

    2013-01-01

    Full Text Available When we talk about severe malaria, we usually think of Plasmodium falciparum. However, in recent times, Plasmodium vivax has also been reported to cause severe multi-organ dysfunction and life-threatening disease similar to P. falciparum. We report here a case of P. vivax malaria in a young boy from an endemic zone, who developed acute renal failure, severe thrombocytopenia, and anemia and later developed spontaneous subarachnoid hemorrhage. Multisystem involvement in a patient with P. vivax is rare, and subarachnoid hemorrhage is an unusual presentation.

  18. Electron microscopic features of brain edema in rodent cerebral malaria in relation to glial fibrillary acidic protein expression.

    Science.gov (United States)

    Ampawong, Sumate; Chaisri, Urai; Viriyavejakul, Parnpen; Nontprasert, Apichart; Grau, Georges E; Pongponratn, Emsri

    2014-01-01

    The mechanisms leading to cerebral malaria (CM) are not completely understood. Brain edema has been suggested as having an important role in experimental CM. In this study, CBA/CaH mice were infected with Plasmodium berghei ANKA blood-stage and when typical symptoms of CM developed on day 7, brain tissues were processed for electron-microscopic and immunohistochemical studies. The study demonstrated ultrastructural hallmarks of cerebral edema by perivascular edema and astroglial dilatation confirming existing evidence of vasogenic and cytogenic edema. This correlates closely with the clinical features of CM. An adaptive response of astrocytic activity, represented by increasing glial fibrillary acidic protein (GFAP) expression in the perivascular area and increasing numbers of large astrocyte clusters were predominately found in the CM mice. The presence of multivesicular and lamellar bodies indicates the severity of cerebral damage in experimental CM. Congestion of the microvessels with occluded white blood cells (WBCs), parasitized red blood cells (PRBCs) and platelets is also a crucial covariate role for CM pathogenesis.

  19. Acute P. falciparum malaria induces a loss of CD28- T IFN-¿ producing cells

    DEFF Research Database (Denmark)

    Kemp, Kåre; Akanmori, Bartholomew D; Kurtzhals, Jørgen A L

    2002-01-01

    P. falciparum malaria is associated with increased activation among peripheral lymphocytes. In the present study, we investigated markers of susceptibility to apoptosis and expression of IFN-gamma and IL-4 by CD28-and CD28+T cells in West African children with acute P. falciparum malaria. The stu...

  20. Efficacy of artesunate-amodiaquine for the treatment of acute uncomplicated falciparum malaria in southern Mauritania.

    Science.gov (United States)

    Ouldabdallahi, Mohamed; Alew, Ismail; Salem, Mohamed Salem Ould Ahmedou; Dit Dialaw Ba, Mamadou; Boukhary, Ali Ould Mohamed Salem; Khairy, Mohamed Lemine Ould; Aziz, Mohamed Boubacar Abdel; Ringwald, Pascal; Basco, Leonardo K; Niang, Saidou Doro; Lebatt, Sid Mohamed

    2014-12-16

    A regular evaluation of therapeutic efficacy in sentinel sites and a system of surveillance are required to establish treatment guidelines and adapt national anti-malarial drug policy to the rapidly changing epidemiology of drug-resistant malaria. The current anti-malarial treatment guideline in Mauritania, officially recommended since 2006, is based on artemisinin-based combination therapy. The aim of the present study was to evaluate clinical efficacy and tolerance of artesunate-amodiaquine, the first-line treatment for acute uncomplicated malaria, in Mauritanian paediatric and adult patients to validate its continued use in the country. Plasmodium falciparum-infected symptomatic patients aged > six months were enrolled in Kobeni and Timbedra in southern Mauritania in September to October 2013. Co-formulated artesunate-amodiaquine was administered at the recommended dose over three days. Patients were followed until day 28. Parasitological and clinical response was classified according to the standard 2009 World Health Organization protocol. A total of 130 patients (65 in Kobeni and 65 in Timbedra) were enrolled in the study. Seventeen patients (13.1%) were either excluded (before PCR correction) or lost to follow-up. Based on the per protocol analysis, artesunate-amodiaquine efficacy (i.e., the proportion of adequate clinical and parasitological response) was 96.6% in Kobeni and 98.2% in Timbedra before PCR correction. Late clinical failure was observed in two patients in Kobeni and one patient in Timbedra. After PCR correction, the efficacy rate in the two study sites was 98.2%. On day 3, all patients were afebrile and had negative smears. Treatment was well tolerated. Artesunate-amodiaquine is well tolerated and highly efficacious for the treatment of uncomplicated P. falciparum malaria. In the majority of patients, fever and parasitaemia were rapidly cleared before day 3. The results support the national anti-malarial drug guideline for a continued use of

  1. Acute partial sleep deprivation due to environmental noise increases weight gain by reducing energy expenditure in rodents.

    Science.gov (United States)

    Parrish, Jennifer B; Teske, Jennifer A

    2017-01-01

    Chronic partial sleep deprivation (SD) by environmental noise exposure increases weight gain and feeding in rodents, which contrasts weight loss after acute SD by physical methods. This study tested whether acute environmental noise exposure reduced sleep and its effect on weight gain, food intake, physical activity, and energy expenditure (EE). It was hypothesized that acute exposure would (1) increase weight gain and feeding and (2) reduce sleep, physical activity, and EE (total and individual components); and (3) behavioral changes would persist throughout recovery from SD. Three-month old male Sprague-Dawley rats slept ad libitum, were noise exposed (12-h light cycle), and allowed to recover (36 h). Weight gain, food intake, sleep/wake, physical activity, and EE were measured. Acute environmental noise exposure had no effect on feeding, increased weight gain (P sleep (P sleep, rest, and physical activity reduce total EE and contribute to weight gain during acute SD and recovery from SD. These data emphasize the importance of increasing physical activity after SD to prevent obesity. © 2016 The Obesity Society.

  2. Early platelet dysfunction in a rodent model of blunt traumatic brain injury reflects the acute traumatic coagulopathy found in humans.

    Science.gov (United States)

    Donahue, Deborah L; Beck, Julia; Fritz, Braxton; Davis, Patrick; Sandoval-Cooper, Mayra J; Thomas, Scott G; Yount, Robert A; Walsh, Mark; Ploplis, Victoria A; Castellino, Francis J

    2014-02-15

    Acute coagulopathy is a serious complication of traumatic brain injury (TBI) and is of uncertain etiology because of the complex nature of TBI. However, recent work has shown a correlation between mortality and abnormal hemostasis resulting from early platelet dysfunction. The aim of the current study was to develop and characterize a rodent model of TBI that mimics the human coagulopathic condition so that mechanisms of the early acute coagulopathy in TBI can be more readily assessed. Studies utilizing a highly reproducible constrained blunt-force brain injury in rats demonstrate a strong correlation with important postinjury pathological changes that are observed in human TBI patients, namely, diminished platelet responses to agonists, especially adenosine diphosphate (ADP), and subarachnoid bleeding. Additionally, administration of a direct thrombin inhibitor, preinjury, recovers platelet functionality to ADP stimulation, indicating a direct role for excess thrombin production in TBI-induced early platelet dysfunction.

  3. Acute renal failure in falciparum malaria: Clinical characteristics, demonstration of oxidative stress, and prognostication

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    Ch. Venkata Rama Krishna

    2012-01-01

    Full Text Available In this prospective study, we aimed to assess the clinical characteristics of acute renal failure (ARF, determine oxidative stress, as well as to predict the outcome in patients with severe falciparum malaria (FM. The study included a total of 75 subjects; there were 25 adult patients with acute severe FM and ARF, 25 adult patients with uncomplicated FM without ARF, and 25 age- and sex-matched healthy subjects who served as controls. In patients with severe FM and ARF (n = 25, renal failure was non-oliguric in 28% and oliguric in 72%. The average duration of renal failure was 10.53 ± 4.0 days. Sixty percent recovered and 40% died. All patients with non-oliguric presentation recovered. The mean serum malondialdehyde (MDA levels were 0.82 ± 0.43 μmol/L, 2.97 ± 1.11 μmol/L, and 6.86 ± 2.62 μmol/L, respectively, in healthy con-trols, in patients with uncomplicated FM, and in those with severe FM with ARF. The Acute Physiology Age and Chronic Health Evaluation II (APACHE II score, Sequential Organ Failure Assessment (SOFA score, and the Acute Tubular Necrosis-Individual Severity Index (ATN-ISI score were all significantly higher in the expired group (19 ± 5.49 when compared to the survivor group (14.4 ± 3.15 (P = 0.014. Kaplan-Meier survival analysis showed that survival was low in patients with delayed hospitalization and longer duration of symptoms. Also, we observed a high occurrence of acute respiratory distress syndrome and central nervous system involvement among the patients who expired.

  4. Transmission blocking activity of a standardized neem (Azadirachta indica) seed extract on the rodent malaria parasite Plasmodium berghei in its vector Anopheles stephensi

    Science.gov (United States)

    2010-01-01

    Background The wide use of gametocytocidal artemisinin-based combination therapy (ACT) lead to a reduction of Plasmodium falciparum transmission in several African endemic settings. An increased impact on malaria burden may be achieved through the development of improved transmission-blocking formulations, including molecules complementing the gametocytocidal effects of artemisinin derivatives and/or acting on Plasmodium stages developing in the vector. Azadirachtin, a limonoid (tetranortriterpenoid) abundant in neem (Azadirachta indica, Meliaceae) seeds, is a promising candidate, inhibiting Plasmodium exflagellation in vitro at low concentrations. This work aimed at assessing the transmission-blocking potential of NeemAzal®, an azadirachtin-enriched extract of neem seeds, using the rodent malaria in vivo model Plasmodium berghei/Anopheles stephensi. Methods Anopheles stephensi females were offered a blood-meal on P. berghei infected, gametocytaemic BALB/c mice, treated intraperitoneally with NeemAzal, one hour before feeding. The transmission-blocking activity of the product was evaluated by assessing oocyst prevalence, oocyst density and capacity to infect healthy mice. To characterize the anti-plasmodial effects of NeemAzal® on early midgut stages, i.e. zygotes and ookinetes, Giemsa-stained mosquito midgut smears were examined. Results NeemAzal® completely blocked P. berghei development in the vector, at an azadirachtin dose of 50 mg/kg mouse body weight. The totally 138 examined, treated mosquitoes (three experimental replications) did not reveal any oocyst and none of the healthy mice exposed to their bites developed parasitaemia. The examination of midgut content smears revealed a reduced number of zygotes and post-zygotic forms and the absence of mature ookinetes in treated mosquitoes. Post-zygotic forms showed several morphological alterations, compatible with the hypothesis of an azadirachtin interference with the functionality of the microtubule

  5. Antimalarial potential of China 30 and Chelidonium 30 in combination therapy against lethal rodent malaria parasite: Plasmodium berghei.

    Science.gov (United States)

    Rajan, Aswathy; Bagai, Upma

    2013-05-07

    Homeopathy is a therapeutic method based on the application of similia principle, utilizing ultra-low doses of medicinal substances made from natural products. The present study has been designed to evaluate the efficacy of Cinchona officinalis (Chin.) 30C and Chelidonium majus (Chel.) 30C in combination therapy against lethal murine malaria. Five groups having twelve BALB/c mice each were administered orally with 0.2 ml/mouse/day of different drugs, and their antimalarial potential was evaluated by Peter's 4-day test. The combination of Chin. 30 and Chel. 30 exhibited complete parasite clearance by the 28th day post-inoculation which was similar to the positive control [artesunate (4 mg/kg)+sulphadoxine-primethamine (1.2 mg/kg)] group. Both the groups exhibited enhanced mean survival time (MST) 28±0 days,whereas, the mice of infected control group survived up to 7.6±0.4 days only. The preventive and curative activities of the combination in comparison to the positive controls [pyrimethamine (1.2 mg/Kg) and chloroquine (20 mg/Kg), respectively] were also evaluated. The combination had a significant preventive activity (p<0.0005), with 89.2% chemosuppression which was higher than the standard drug, pyrimethamine (83.8%). It also showed a moderate curative activity with complete clearance of parasite in 50% of surviving mice, and enhancing the MST of mice up to 26.8±2.8 days. These findings point to the significant antiplasmodial efficacy of the combination of these homeopathic drugs against Plasmodium berghei.

  6. Acute HIV-1 infection is as common as malaria in young febrile adults seeking care in coastal Kenya.

    Science.gov (United States)

    Sanders, Eduard J; Mugo, Peter; Prins, Henrieke A B; Wahome, Elizabeth; Thiong'o, Alexander N; Mwashigadi, Grace; van der Elst, Elisabeth M; Omar, Anisa; Smith, Adrian D; Graham, Susan M

    2014-06-01

    Febrile adults are usually not tested for acute HIV-1 infection (AHI) in Africa. We assessed a strategy to diagnose AHI among young adult patients seeking care. Young adults (malaria using a rapid test, with PCR confirmation of positives. In 3602 adults seeking care, overall HIV-1 prevalence was 3.9%: 7.6% (68/897) among patients meeting AHI criteria vs. 2.6% (71/2705) among those who did not (P Malaria was confirmed by PCR in four (1.7%) of the 241 febrile patients. AHI was as common as confirmed malaria in young febrile adults seeking care. An AHI detection strategy targeting young febrile adults seeking care at pharmacies and health facilities is feasible and should be considered as an HIV-prevention strategy in high-transmission settings.

  7. Identification and sequencing of a novel rodent gammaherpesvirus that establishes acute and latent infection in laboratory mice.

    Science.gov (United States)

    Loh, Joy; Zhao, Guoyan; Nelson, Christopher A; Coder, Penny; Droit, Lindsay; Handley, Scott A; Johnson, L Steven; Vachharajani, Punit; Guzman, Hilda; Tesh, Robert B; Wang, David; Fremont, Daved H; Virgin, Herbert W

    2011-03-01

    Gammaherpesviruses encode numerous immunomodulatory molecules that contribute to their ability to evade the host immune response and establish persistent, lifelong infections. As the human gammaherpesviruses are strictly species specific, small animal models of gammaherpesvirus infection, such as murine gammaherpesvirus 68 (γHV68) infection, are important for studying the roles of gammaherpesvirus immune evasion genes in in vivo infection and pathogenesis. We report here the genome sequence and characterization of a novel rodent gammaherpesvirus, designated rodent herpesvirus Peru (RHVP), that shares conserved genes and genome organization with γHV68 and the primate gammaherpesviruses but is phylogenetically distinct from γHV68. RHVP establishes acute and latent infection in laboratory mice. Additionally, RHVP contains multiple open reading frames (ORFs) not present in γHV68 that have sequence similarity to primate gammaherpesvirus immunomodulatory genes or cellular genes. These include ORFs with similarity to major histocompatibility complex class I (MHC-I), C-type lectins, and the mouse mammary tumor virus and herpesvirus saimiri superantigens. As these ORFs may function as immunomodulatory or virulence factors, RHVP presents new opportunities for the study of mechanisms of immune evasion by gammaherpesviruses.

  8. Human T cell recognition of the blood stage antigen Plasmodium hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT in acute malaria

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    Woodberry Tonia

    2009-06-01

    Full Text Available Abstract Background The Plasmodium purine salvage enzyme, hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT can protect mice against Plasmodium yoelii pRBC challenge in a T cell-dependent manner and has, therefore, been proposed as a novel vaccine candidate. It is not known whether natural exposure to Plasmodium falciparum stimulates HGXPRT T cell reactivity in humans. Methods PBMC and plasma collected from malaria-exposed Indonesians during infection and 7–28 days after anti-malarial therapy, were assessed for HGXPRT recognition using CFSE proliferation, IFNγ ELISPOT assay and ELISA. Results HGXPRT-specific T cell proliferation was found in 44% of patients during acute infection; in 80% of responders both CD4+ and CD8+ T cell subsets proliferated. Antigen-specific T cell proliferation was largely lost within 28 days of parasite clearance. HGXPRT-specific IFN-γ production was more frequent 28 days after treatment than during acute infection. HGXPRT-specific plasma IgG was undetectable even in individuals exposed to malaria for at least two years. Conclusion The prevalence of acute proliferative and convalescent IFNγ responses to HGXPRT demonstrates cellular immunogenicity in humans. Further studies to determine minimal HGXPRT epitopes, the specificity of responses for Plasmodia and associations with protection are required. Frequent and robust T cell proliferation, high sequence conservation among Plasmodium species and absent IgG responses distinguish HGXPRT from other malaria antigens.

  9. A distinct peripheral blood monocyte phenotype is associated with parasite inhibitory activity in acute uncomplicated Plasmodium falciparum malaria.

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    Pattamawan Chimma

    2009-10-01

    Full Text Available Monocyte (MO subpopulations display distinct phenotypes and functions which can drastically change during inflammatory states. We hypothesized that discrete MO subpopulations are induced during malaria infection and associated with anti-parasitic activity. We characterized the phenotype of blood MO from healthy malaria-exposed individuals and that of patients with acute uncomplicated malaria by flow cytometry. In addition, MO defense function was evaluated by an in vitro antibody dependent cellular inhibition (ADCI assay. At the time of admission, the percentages and absolute numbers of CD16+ MO, and CCR2+CX3CR1+ MO, were high in a majority of patients. Remarkably, expression of CCR2 and CX3CR1 on the CD14(high (hi MO subset defined two subgroups of patients that also differed significantly in their functional ability to limit the parasite growth, through the ADCI mechanism. In the group of patients with the highest percentages and absolute numbers of CD14(hiCCR2+CX3CR1+ MO and the highest mean levels of ADCI activity, blood parasitemias were lower (0.14+/-0.34% than in the second group (1.30+/-3.34%; p = 0.0053. Data showed that, during a malaria attack, some patients' MO can exert a strong ADCI activity. These results bring new insight into the complex relationships between the phenotype and the functional activity of blood MO from patients and healthy malaria-exposed individuals and suggest discrete MO subpopulations are induced during malaria infection and are associated with anti-parasitic activity.

  10. Forecasting non-stationary diarrhea, acute respiratory infection, and malaria time-series in Niono, Mali.

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    Daniel C Medina

    Full Text Available BACKGROUND: Much of the developing world, particularly sub-Saharan Africa, exhibits high levels of morbidity and mortality associated with diarrhea, acute respiratory infection, and malaria. With the increasing awareness that the aforementioned infectious diseases impose an enormous burden on developing countries, public health programs therein could benefit from parsimonious general-purpose forecasting methods to enhance infectious disease intervention. Unfortunately, these disease time-series often i suffer from non-stationarity; ii exhibit large inter-annual plus seasonal fluctuations; and, iii require disease-specific tailoring of forecasting methods. METHODOLOGY/PRINCIPAL FINDINGS: In this longitudinal retrospective (01/1996-06/2004 investigation, diarrhea, acute respiratory infection of the lower tract, and malaria consultation time-series are fitted with a general-purpose econometric method, namely the multiplicative Holt-Winters, to produce contemporaneous on-line forecasts for the district of Niono, Mali. This method accommodates seasonal, as well as inter-annual, fluctuations and produces reasonably accurate median 2- and 3-month horizon forecasts for these non-stationary time-series, i.e., 92% of the 24 time-series forecasts generated (2 forecast horizons, 3 diseases, and 4 age categories = 24 time-series forecasts have mean absolute percentage errors circa 25%. CONCLUSIONS/SIGNIFICANCE: The multiplicative Holt-Winters forecasting method: i performs well across diseases with dramatically distinct transmission modes and hence it is a strong general-purpose forecasting method candidate for non-stationary epidemiological time-series; ii obliquely captures prior non-linear interactions between climate and the aforementioned disease dynamics thus, obviating the need for more complex disease-specific climate-based parametric forecasting methods in the district of Niono; furthermore, iii readily decomposes time-series into seasonal

  11. CD8+ T cells from a novel T cell receptor transgenic mouse induce liver-stage immunity that can be boosted by blood-stage infection in rodent malaria.

    Science.gov (United States)

    Lau, Lei Shong; Fernandez-Ruiz, Daniel; Mollard, Vanessa; Sturm, Angelika; Neller, Michelle A; Cozijnsen, Anton; Gregory, Julia L; Davey, Gayle M; Jones, Claerwen M; Lin, Yi-Hsuan; Haque, Ashraful; Engwerda, Christian R; Nie, Catherine Q; Hansen, Diana S; Murphy, Kenneth M; Papenfuss, Anthony T; Miles, John J; Burrows, Scott R; de Koning-Ward, Tania; McFadden, Geoffrey I; Carbone, Francis R; Crabb, Brendan S; Heath, William R

    2014-05-01

    To follow the fate of CD8+ T cells responsive to Plasmodium berghei ANKA (PbA) infection, we generated an MHC I-restricted TCR transgenic mouse line against this pathogen. T cells from this line, termed PbT-I T cells, were able to respond to blood-stage infection by PbA and two other rodent malaria species, P. yoelii XNL and P. chabaudi AS. These PbT-I T cells were also able to respond to sporozoites and to protect mice from liver-stage infection. Examination of the requirements for priming after intravenous administration of irradiated sporozoites, an effective vaccination approach, showed that the spleen rather than the liver was the main site of priming and that responses depended on CD8α+ dendritic cells. Importantly, sequential exposure to irradiated sporozoites followed two days later by blood-stage infection led to augmented PbT-I T cell expansion. These findings indicate that PbT-I T cells are a highly versatile tool for studying multiple stages and species of rodent malaria and suggest that cross-stage reactive CD8+ T cells may be utilized in liver-stage vaccine design to enable boosting by blood-stage infections.

  12. Oliguric and non-oliguric acute renal failure in malaria in west zone of rajasthan, India-A comparative study

    Institute of Scientific and Technical Information of China (English)

    Bal Kishan Gupta; Kailash Chandra Nayak; Sunil Kumar; Surendra Kumar; Anjli Gupta; Parul Prakash

    2012-01-01

    Objective: To report a comparative clinical and histopathological study on oliguric and non-oliguric acute renal failure (ARF) in malaria. Method: 311 consecutive cases of malaria out of which 74 (23.79%) had ARF as per WHO criteria were conducted. Mean age was 32.58 (range 15-60 years) and male: female was 2:1. Result: Most of the cases developed ARF within 10 d of onset. 18 cases (11 falciparum, 2 mixed, 5 vivax) presented with oliguric and 56 (41 falciparum, 6 mixed, 9 vivax) with non-oliguric renal failure. Associated major manifestations were jaundice (75.68%), cerebral malaria (41.89%), bleeding manifestations (32.43%), severe anemia (27.03%), hypotension (25.68%), multi-organ failure (18.92%), severe thrombocytopenia (12.16%), and ARDS (8.11%). Kidney biopsy (n=20) showed acute tubular necrosis (n=7), Mesangioproliferative glomerulonephritis (n=4) or both (n=9). Hemodialysis was done in 8 cases of oliguric renal failure out of which 4 survived (average no. of session 2.9). Conclusion: Most of the cases recovered within 3 weeks. Total mortality was 28.38% (n=21) and mortality was more in oliguric renal failure (72.22%) as compare to non-oliguric renal failure (14.29%).

  13. Impact of acute vivax malaria on the immune system and viral load of HIV-positive subjects

    Institute of Scientific and Technical Information of China (English)

    陈小平; 肖斌权; 施文钧; 徐慧芳; 高凯; 饶纪礼; 张周斌

    2003-01-01

    Objective To explore the mechanisms of malariotherapy for human immunodeficiency virus (HIV)-infected patients and to identify which stage(s) of HIV infection is suitable for the treatment of malariotherapy.Methods Therapeutic acute vivax malaria was induced and terminated after 10 fever episodes in 12 HIV-1-infected subjects: Group 1 (G1) had 5 patients with CD4 T-cell counts500/μl at baseline, Group 2 (G2) had 5 patients with CD4 at 499-200/μl and Group 3 had 2 patients with CD4<200/μl (not included in statistical analysis). Enzyme-Linked-Immuno-Sorbent Assay (ELISA) was used to measure plasma levels of cytokines and soluble activation markers. Flow cytometry was used to measure levels of lymphocyte subsets and phenotypes and CD4 cell apoptosis. Bayer bDNA assay was used to test plasma levels of HIV-1 RNA (viral load). Samples were taken and tested twice before malaria (baselines), three times during malaria and seven times after termination of malaria (at day 10 and 1, 3, 6, 12, 18 and 24 months). Results Levels of plasma tumor necrosis factor-α (TNF-α), soluble TNF-α receptor-2 (sTNF-RII), neopterin (NPT) and soluble IL-2 receptor (sIL-2R) significantly increased during malaria and sharply reduced to baselines post malaria in all groups. Stronger responses of the aforementioned factors were seen in G2 than in G1 during malaria (P=0.081, 0.001, 0.013, 0.020). CD4 count and percentage; CD4/CD8 ratio and CD25+ and CD4+CD25+ percentages increased but HLA DR+ percentage decreased either during or post malaria in G2. Most G2 patients experienced sustained increase but most G1 patients underwent natural history decline of CD4 counts and percentages during 2-year follow-up. Percentage of apoptotic CD4 cells decreased post malaria in all groups. G3 patients had weaker immune responses, however, one advanced AIDS patient in this group experienced clinical improvement after malariotherapy. Most of the 12 patients experienced increase of HIV viral load during

  14. Aldehyde dehydrogenase-2 regulates nociception in rodent models of acute inflammatory pain.

    Science.gov (United States)

    Zambelli, Vanessa O; Gross, Eric R; Chen, Che-Hong; Gutierrez, Vanessa P; Cury, Yara; Mochly-Rosen, Daria

    2014-08-27

    Exogenous aldehydes can cause pain in animal models, suggesting that aldehyde dehydrogenase-2 (ALDH2), which metabolizes many aldehydes, may regulate nociception. To test this hypothesis, we generated a knock-in mouse with an inactivating point mutation in ALDH2 (ALDH2*2), which is also present in human ALDH2 of ~540 million East Asians. The ALDH2*1/*2 heterozygotic mice exhibited a larger response to painful stimuli than their wild-type littermates, and this heightened nociception was inhibited by an ALDH2-selective activator (Alda-1). No effect on inflammation per se was observed. Using a rat model, we then showed that nociception tightly correlated with ALDH activity (R(2) = 0.90) and that reduced nociception was associated with less early growth response protein 1 (EGR1) in the spinal cord and less reactive aldehyde accumulation at the insult site (including acetaldehyde and 4-hydroxynonenal). Further, acetaldehyde- and formalin-induced nociceptive behavior was greater in the ALDH2*1/*2 mice than in the wild-type mice. Finally, Alda-1 treatment was even beneficial when given after the inflammatory agent was administered. Our data in rodent models suggest that the mitochondrial enzyme ALDH2 regulates nociception and could serve as a molecular target for pain control, with ALDH2 activators, such as Alda-1, as potential non-narcotic, cardiac-safe analgesics. Furthermore, our results suggest a possible genetic basis for East Asians' apparent lower pain tolerance.

  15. A Child with Severe Malaria Presenting with Acute Surgical Abdomen (Duodenal Perforation

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    Tika Ram Bhandari

    2016-01-01

    Full Text Available Plasmodium falciparum, the commonest cause of severe malaria in children, is an important cause of mortality in developing nations like Nepal. Duodenal perforation in a case of complicated malaria, although a rare entity, can occur in children. Early diagnosis, proper medical treatment, and early surgical repair can be a lifesaving measure in such cases. Here, we report a case of a 5-year-old male child with falciparum malaria complicated by a duodenal perforation that was successively managed with appropriate antimalarial drugs and early surgical repair.

  16. A Child with Severe Malaria Presenting with Acute Surgical Abdomen (Duodenal Perforation).

    Science.gov (United States)

    Bhandari, Tika Ram; Shahi, Sudha; Poudel, Rajesh; Chaudhary, Nagendra

    2016-01-01

    Plasmodium falciparum, the commonest cause of severe malaria in children, is an important cause of mortality in developing nations like Nepal. Duodenal perforation in a case of complicated malaria, although a rare entity, can occur in children. Early diagnosis, proper medical treatment, and early surgical repair can be a lifesaving measure in such cases. Here, we report a case of a 5-year-old male child with falciparum malaria complicated by a duodenal perforation that was successively managed with appropriate antimalarial drugs and early surgical repair.

  17. Acute and Chronic Toxicity of an Aqueous Fraction of the Stem Bark of Stryphnodendron adstringens (Barbatimão) in Rodents.

    Science.gov (United States)

    Costa, Marco Antonio; Palazzo de Mello, João Carlos; Kaneshima, Edílson Nobuyoshi; Ueda-Nakamura, Tânia; Dias Filho, Benedito Prado; Audi, Elisabeth Aparecida; Nakamura, Celso Vataru

    2013-01-01

    Stryphnodendron adstringens has a high tannin content and is used as an antiseptic and antimicrobial and in the treatment of leucorrhea, gonorrhea, wound healing, and gastritis. The present study evaluated the toxic effects of the heptamer prodelphinidin (F2) from the stem bark of S. adstringens in rodents. In the acute toxicity test, the mice that received oral doses exhibited reversible effects, with an LD50 of 3.015 mg · kg(-1). In the chronic toxicity test at 90 days, Wistar rats were treated with different doses of F2 (10, 100, and 200 mg · kg(-1)). In the biochemical, hematological, and histopathological examinations and open-field test, the different dose groups did not exhibit significant differences compared with controls. The present results indicate that F2 from the stem bark of S. adstringens caused no toxicity with acute and chronic oral treatment in rodents at the doses administered.

  18. Acute and Chronic Toxicity of an Aqueous Fraction of the Stem Bark of Stryphnodendron adstringens (Barbatimão in Rodents

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    Marco Antonio Costa

    2013-01-01

    Full Text Available Stryphnodendron adstringens has a high tannin content and is used as an antiseptic and antimicrobial and in the treatment of leucorrhea, gonorrhea, wound healing, and gastritis. The present study evaluated the toxic effects of the heptamer prodelphinidin (F2 from the stem bark of S. adstringens in rodents. In the acute toxicity test, the mice that received oral doses exhibited reversible effects, with an LD50 of 3.015 mg·kg−1. In the chronic toxicity test at 90 days, Wistar rats were treated with different doses of F2 (10, 100, and 200 mg·kg−1. In the biochemical, hematological, and histopathological examinations and open-field test, the different dose groups did not exhibit significant differences compared with controls. The present results indicate that F2 from the stem bark of S. adstringens caused no toxicity with acute and chronic oral treatment in rodents at the doses administered.

  19. Acute and Chronic Toxicity of an Aqueous Fraction of the Stem Bark of Stryphnodendron adstringens (Barbatimão) in Rodents

    Science.gov (United States)

    Costa, Marco Antonio; Palazzo de Mello, João Carlos; Kaneshima, Edílson Nobuyoshi; Ueda-Nakamura, Tânia; Dias Filho, Benedito Prado; Audi, Elisabeth Aparecida

    2013-01-01

    Stryphnodendron adstringens has a high tannin content and is used as an antiseptic and antimicrobial and in the treatment of leucorrhea, gonorrhea, wound healing, and gastritis. The present study evaluated the toxic effects of the heptamer prodelphinidin (F2) from the stem bark of S. adstringens in rodents. In the acute toxicity test, the mice that received oral doses exhibited reversible effects, with an LD50 of 3.015 mg · kg−1. In the chronic toxicity test at 90 days, Wistar rats were treated with different doses of F2 (10, 100, and 200 mg · kg−1). In the biochemical, hematological, and histopathological examinations and open-field test, the different dose groups did not exhibit significant differences compared with controls. The present results indicate that F2 from the stem bark of S. adstringens caused no toxicity with acute and chronic oral treatment in rodents at the doses administered. PMID:23970938

  20. Acute and subchronic toxicity assessment model of Ferula assa-foetida gum in rodents

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    Ayman Goudah

    2015-05-01

    Full Text Available Aim: The present study was performed to investigate acute and subchronic oral toxicity of Ferula assa-foetida gum (28 days in Sprague Dawley rats. Materials and Methods: Acute oral administration of F. assa-foetida was done as a single bolus dose up to 5 g/kg in mice and subchronic toxicity study for 28 days was done by oral administration at doses of 0 (control and 250 mg/kg in Sprague Dawley rats. Results: The obtained data revealed that oral administration of F. assa-foetida extract in rats for 28 successive days had no significant changes on body weight, body weight gain, the hematological parameters in rats all over the period of the experiment, and there are no significant increases in the activity of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine and urea. Liver of treated rats showed mild changes as thrombosis and sinusoidal leukocytosis. It also showed portal infiltration with inflammatory cells, while kidney of treated rat showed an atrophy of glomerular tuft, thickening of parietal layer of Bowman capsule, and focal tubular necrosis. It also showed dilatation and congestion of renal blood vessels. Conclusion: We concluded that F. assa-foetida gum had broad safety and little toxicity for short term use in dose of 250 mg/kg.

  1. Kynurenine–3–monooxygenase inhibition prevents multiple organ failure in rodent models of acute pancreatitis

    Science.gov (United States)

    Mole, Damian J; Webster, Scott P; Uings, Iain; Zheng, Xiaozhong; Binnie, Margaret; Wilson, Kris; Hutchinson, Jonathan P; Mirguet, Olivier; Walker, Ann; Beaufils, Benjamin; Ancellin, Nicolas; Trottet, Lionel; Bénéton, Véronique; Mowat, Christopher G; Wilkinson, Martin; Rowland, Paul; Haslam, Carl; McBride, Andrew; Homer, Natalie ZM; Baily, James E; Sharp, Matthew GF; Garden, O James; Hughes, Jeremy; Howie, Sarah EM; Holmes, Duncan S; Liddle, John; Iredale, John P

    2015-01-01

    Acute pancreatitis (AP) is a common and devastating inflammatory condition of the pancreas that is considered to be a paradigm of sterile inflammation leading to systemic multiple organ dysfunction syndrome (MODS) and death1,2 Acute mortality from AP-MODS exceeds 20%3 and for those who survive the initial episode, their lifespan is typically shorter than the general population4. There are no specific therapies available that protect individuals against AP-MODS. Here, we show that kynurenine-3-monooxygenase (KMO), a key enzyme of tryptophan metabolism5, is central to the pathogenesis of AP-MODS. We created a mouse strain deficient for Kmo with a robust biochemical phenotype that protected against extrapancreatic tissue injury to lung, kidney and liver in experimental AP-MODS. A medicinal chemistry strategy based on modifications of the kynurenine substrate led to the discovery of GSK180 as a potent and specific inhibitor of KMO. The binding mode of the inhibitor in the active site was confirmed by X-ray co-crystallography at 3.2 Å resolution. Treatment with GSK180 resulted in rapid changes in levels of kynurenine pathway metabolites in vivo and afforded therapeutic protection against AP-MODS in a rat model of AP. Our findings establish KMO inhibition as a novel therapeutic strategy in the treatment of AP-MODS and open up a new area for drug discovery in critical illness. PMID:26752518

  2. Efficient monitoring of blood-stage infection in a malaria rodent model by the rotating-crystal magneto-optical method

    CERN Document Server

    Orban, Agnes; Albuquerque, Inês S; Butykai, Adam; Kezsmarki, Istvan; Hänscheid, Thomas

    2015-01-01

    Global research efforts have been focused on the simultaneous improvement of the efficiency and sensitivity of malaria diagnosis in resource-limited settings and for the active case detection of asymptomatic infections. A recently developed magneto-optical (MO) method allows the high-sensitivity detection of malaria pigment (hemozoin) crystals in blood via their magnetically induced rotational motion. The evaluation of the method using synthetic $\\beta$-hematin crystals and P. falciparum in vitro cultures implies its potential for in-field diagnosis. Here, we study the performance of the method in monitoring the in vivo onset and progression of the blood stage infection using a malaria mouse model. We found that the MO method can detect the first generation of intraerythrocytic parasites at the ring stage 61-66 hours after sporozoite injection demonstrating better sensitivity than light microscopy and flow cytometry. MO measurements performed after treatment of severe P. berghei infections show that the clear...

  3. Atovaquone and proguanil hydrochloride compared with chloroquine or pyrimethamine/sulfadoxine for treatment of acute Plasmodium falciparum malaria in Peru

    Directory of Open Access Journals (Sweden)

    Llanos-Cuentas A.

    2001-01-01

    Full Text Available The efficacy and safety of a fixed-dose combination of atovaquone and proguanil hydrochloride (MalaroneTM were compared with chloroquine or pyrimethamine/sulfadoxine in patients with acute falciparum malaria in northern Peru. Patients were initially randomized to receive 1,000 mg atovaquone and 400 mg proguanil hydrochloride daily for 3 days (n=15 or 1,500 mg chloroquine (base over a 3 day period (n=14 (phase 1. The cure rate with chloroquine was lower than expected and patients were subsequently randomized to receive a single dose of 75 mg pyrimethamine and 1,500 mg sulfadoxine (n=9 or atovaquone/proguanil as before (n=5 (phase 2. In phase 1, atovaquone/proguanil was significantly more effective than chloroquine (cure rate 100% [14/14] versus 8% [1/13], P<0.0001. In phase 2, atovaquone/proguanil and pyrimethamine/sulfadoxine were both highly effective (cure rates 100% [5/5] and 100% [7/7]. There were no significant differences between treatment groups in parasite or fever clearance times. Adverse events were typical of malarial symptoms and did not differ significantly between groups. Overall efficacy of atovaquone/proguanil was 100% for treatment of acute falciparum malaria in a region with a high prevalence of chloroquine resistance.

  4. Malaria in Pregnancy

    Directory of Open Access Journals (Sweden)

    E E Okpere

    2010-01-01

    Full Text Available Malaria remains one of the highest contributors to the precarious maternal mortality figures in sub-Saharan Africa. At least 6 million women worldwide are at risk of malaria infection in pregnancy. Malaria contributes to at least 10, 000 maternal deaths and to at least 200, 000 newborn deaths annually. Malaria is a contributor or aetiologic factor in pregnancy complications including anaemia, spontaneous abortion, prematurity and stillbirths. Pregnancy results in increased incidence and severity of malaria. Cerebral malaria, acute renal failure and severe anaemia, rare complications in adults living in malaria endemic areas, may complicate malaria in pregnancy. Research implicate reduced maternal immunity from increased steroid levels in pregnancy, increased attractiveness of pregnant women to mosquito bites and increased adherence of parasitized erythrocytes to Chondroitin sulphate A expressed in the placentae. This is worse in the first and second pregnancies. With infection with the Human Immunodeficiency Virus [HIV], the effects of malaria in pregnancy are even worse. Over the decades, there have been concerted worldwide collaborative efforts, spearheaded by the World Health Organization [WHO] and including governments and allied agencies to tackle the scourge of malaria in pregnancy. The main thrusts of such efforts have been: to increase the use of insecticide treated mosquito bed nets [ITN]; intermittent preventive treatment of malaria [IPT]; and adequate case treatment of acute malaria attacks in pregnancy. While for IPT, Sulfadoxine-Pyrimethamine [SP] combination has been proven to be of benefit in preventing acute and latent malaria in pregnancy and its associated complications, the WHO has introduced the use of Artemisinin-Combination Therapy [ACT] for the first-line treatment of uncomplicated malaria in pregnancy, the need to confirm malaria before treatment and the enforcement of completion of therapy once started. The Roll Back

  5. A randomized trial of artesunate-amodiaquine versus artemether-lumefantrine in Ghanaian paediatric sickle cell and non-sickle cell disease patients with acute uncomplicated malaria

    DEFF Research Database (Denmark)

    Adjei, George O; Goka, Bamenla Q; Enweronu-Laryea, Christabel C

    2014-01-01

    BACKGROUND: Sickle cell disease (SCD) is a genetic disorder common in malaria endemic areas. In endemic areas, malaria is a major cause of morbidity and mortality among SCD patients. This suggests the need for prompt initiation of efficacious anti-malarial therapy in SCD patients with acute malaria....../57) in the SCD group and 96.4% (53/55) in the non-SCD group. The fractional changes in haemoglobin, platelets and white blood cell counts between baseline (day 0) and endpoint (day 42) were 16.9, 40.6 and 92.3%, respectively, for the SCD group, and, 12.3, 48.8 and 7.5%, respectively, for the non-SCD group...

  6. T-Regulatory Cells and Inflammatory and Inhibitory Cytokines in Malawian Children Residing in an Area of High and an Area of Low Malaria Transmission During Acute Uncomplicated Malaria and in Convalescence.

    Science.gov (United States)

    Nyirenda, Tonney S; Molyneux, Malcolm E; Kenefeck, Rupert; Walker, Lucy S K; MacLennan, Calman A; Heyderman, Robert S; Mandala, Wilson L

    2015-09-01

    Malaria still infects many Malawian children, and it is a cause of death in some of them. Regulatory T cells (Tregs) help in negating immune-related pathology, it but can also favor multiplication of malaria parasites. The question remains whether children recovering from uncomplicated malaria (UCM) have higher Tregs and interleukin (IL)-10 levels in convalescence. We recruited children between the ages of 6 and 60 months presenting with acute UCM in Blantyre (low transmission area) and Chikwawa (high transmission area). We observed the children after 1 month and 3 months and analyzed their blood samples for parasitemia, lymphocyte subsets, and levels of the cytokines interferon (IFN)-γ, IL-10, and transforming growth factor (TGF)-β. Blood samples from age-matched controls were also analyzed for the same parameters. Compared with controls, acute UCM was associated with mild lymphopenia, splenomegaly, and high levels of IFN-γ, tumor necrosis factor-α, and IL-10, which normalized in convalescence. In Chikwawa, Treg counts were significantly (P effect on parasite clearance. We recommend that children recovering from UCM, especially those from high transmission area, should sleep under insecticide-treated nets, be screened for parasitemia, and a provision of antimalarial prophylaxis should be considered.

  7. Resistance of a rodent malaria parasite to a thymidylate synthase inhibitor induces an apoptotic parasite death and imposes a huge cost of fitness.

    Directory of Open Access Journals (Sweden)

    Francis W Muregi

    Full Text Available BACKGROUND: The greatest impediment to effective malaria control is drug resistance in Plasmodium falciparum, and thus understanding how resistance impacts on the parasite's fitness and pathogenicity may aid in malaria control strategy. METHODOLOGY/PRINCIPAL FINDINGS: To generate resistance, P. berghei NK65 was subjected to 5-fluoroorotate (FOA, an inhibitor of thymidylate synthase, TS pressure in mice. After 15 generations of drug pressure, the 2% DT (the delay time for proliferation of parasites to 2% parasitaemia, relative to untreated wild-type controls reduced from 8 days to 4, equalling the controls. Drug sensitivity studies confirmed that FOA-resistance was stable. During serial passaging in the absence of drug, resistant parasite maintained low growth rates (parasitaemia, 15.5%±2.9, 7 dpi relative to the wild-type (45.6%±8.4, translating into resistance cost of fitness of 66.0%. The resistant parasite showed an apoptosis-like death, as confirmed by light and transmission electron microscopy and corroborated by oligonucleosomal DNA fragmentation. CONCLUSIONS/SIGNIFICANCE: The resistant parasite was less fit than the wild-type, which implies that in the absence of drug pressure in the field, the wild-type alleles may expand and allow drugs withdrawn due to resistance to be reintroduced. FOA resistance led to depleted dTTP pools, causing thymineless parasite death via apoptosis. This supports the tenet that unicellular eukaryotes, like metazoans, also undergo apoptosis. This is the first report where resistance to a chemical stimulus and not the stimulus itself is shown to induce apoptosis in a unicellular parasite. This finding is relevant in cancer therapy, since thymineless cell death induced by resistance to TS-inhibitors can further be optimized via inhibition of pyrimidine salvage enzymes, thus providing a synergistic impact. We conclude that since apoptosis is a process that can be pharmacologically modulated, the parasite

  8. Malaria Facts

    Science.gov (United States)

    ... CDC Malaria Branch clinician. malaria@cdc.gov Malaria Facts Recommend on Facebook Tweet Share Compartir Malaria in ... to determine definitively which species are involved. Other Facts Five times, the Nobel Prize in Physiology or ...

  9. Effects of antifolates - co-trimoxazole and pyrimethamine-sulfadoxine - on gametocytes in children with acute, symptomatic, uncomplicated, Plasmodium falciparum malaria

    Directory of Open Access Journals (Sweden)

    A Sowunmi

    2005-07-01

    Full Text Available Antimalarial drugs including the antifolate, pyrimethamine-sulfadoxine (PS, can modulate the prevalence and intensities of gametocytaemia following treatment of acute malaria infections. They may also directly influence the transmission and spread of drug insensitivity. Little is known of the effects of co-trimoxazole (Co-T, another antifolate antimalarial, on gametocytes in children with acute malaria infections. We compared the effects of Co-T and PS on the prevalence and intensities of gametocytaemia and gametocyte sex ratios in 102 children aged 0.5-12 years presenting with acute and uncomplicated falciparum malaria. Compared to pre-treatment, both drugs significantly increased gametocyte carriage post-initiation of treatment. However, gametocyte carriage was significantly lower on day 14 in those treated with Co-T than PS. Significant increase in gametocytaemia with time occurred in PS - but not Co-T-treated children. Kaplan-Meier survival curve of the cumulative probability of remaining gametocyte-free in children who were agametocytaemic at enrolment showed that by day 7 of follow up, children treated with PS had a significantly higher propensity to have developed gametocytes than in Co-T-treated children (Log-rank statistic 5.35, df = 1, P = 0.02. Gametocyte sex ratio changes were similar following treatment with both drugs. PS and Co-T treatment of acute malaria infections in children from this endemic area is associated with significant increases in prevalence and intensities of gametocytaemia but these effects are more marked in those treated with PS than Co-T.

  10. Optical electrocorticogram (OECoG) using wide-field calcium imaging reveals the divergence of neuronal and glial activity during acute rodent seizures.

    Science.gov (United States)

    Daniel, Andy G S; Laffont, Philippe; Zhao, Mingrui; Ma, Hongtao; Schwartz, Theodore H

    2015-08-01

    The role of glia in epilepsy has been widely debated. Using in vivo bulk loading of calcium dyes, we imaged neuronal and glial activity in an acute pharmacologic rodent model of neocortical seizures. Optical calcium-based ECoG maps revealed that neuronal waves propagated rapidly and remained mostly confined to the seizure focus. Glial waves were triggered by ictal onset but propagated slowly in a stereotypical fashion far beyond the seizure focus. Although related at their onset, the divergence of these two phenomena during seizure evolution calls into question their interdependence and the criticality of the role of glia in seizure onset and neurovascular coupling. This article is part of a Special Issue entitled "Status Epilepticus".

  11. Short report: Role of viruses in Kenyan children presenting with acute encephalopathy in a malaria-endemic area

    NARCIS (Netherlands)

    C.D. Schubart; N. Mturi; M.G.H.M. Beld; P.M. Wertheim; C.R.J.C. Newton

    2006-01-01

    In malaria-endemic areas, it is difficult to differentiate between cerebral malaria (CM), bacterial meningitis, and viral encephalitis. We examined the cerebrospinal fluid of 49 children who fulfilled the World Health Organization's (WHO) definition of CM and in 47 encephalopathic children, without

  12. Acute and sub-chronic oral toxicity studies of an aqueous stem bark extract of Pterocarpus soyauxii Taub (Papilionaceae) in rodents.

    Science.gov (United States)

    Tchamadeu, M C; Dzeufiet, P D D; Nana, P; Kouambou Nouga, C C; Ngueguim Tsofack, F; Allard, J; Blaes, N; Siagat, R; Zapfack, L; Girolami, J P; Tack, I; Kamtchouing, P; Dimo, T

    2011-01-27

    Pterocarpus soyauxii Taub (Papilionaceae) is used in Cameroonian traditional medicine and pharmacopoeia to treat hypertension, diabetes, gastrointestinal parasitizes and cutaneous diseases. The present investigation was carried out to evaluate the safety of an aqueous stem bark extract of Pterocarpus soyauxii by determining toxicity after acute and sub-chronic oral administration in male and female rodents. The acute toxicity test was conducted in mice. An aqueous extract of barks was administrated by gavage in single doses of 2.5-12.5 g/kg. General behaviour and mortality were examined for up to 7 days. The sub-chronic toxicity test was performed in rats. The plant extract was administered by daily gavage of 150-600 mg/kg for 42 days. Body weight, food and water intakes were followed weekly. Haematological, biochemical and organ parameters were determined at the end of the 42-day administration. In the acute study in mice, oral administration of the aqueous extract of Pterocarpus soyauxii caused dose-dependent general behaviour adverse effects and mortality. The no-observed adverse effect level (NOAEL) of the extract was 5.0 g/kg. The lowest-observed adverse effect level (LOAEL) was 7.5 mg/kg. Mortality increased with the dose, LD(50) was>10.75 g/kg for the mouse. In the sub-chronic study in rats, daily oral administration of the aqueous extract of Pterocarpus soyauxii did not result in death or significant changes in haematological or biochemical parameters, excepted increased hepatic catalase activity (PPterocarpus soyauxii Taub had very low toxicity in oral acute high dose administration and no toxicity in oral sub-chronic low dose administration and indicate that the plant could be considered safe for oral medication. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  13. Malaria and Vascular Endothelium

    Energy Technology Data Exchange (ETDEWEB)

    Alencar, Aristóteles Comte Filho de, E-mail: aristoteles.caf@gmail.com [Universidade Federal do Amazonas, Manaus, AM (Brazil); Lacerda, Marcus Vinícius Guimarães de [Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD), Manaus, AM (Brazil); Okoshi, Katashi; Okoshi, Marina Politi [Faculdade de Medicina de Botucatu (Unesp), Botucatu, SP (Brazil)

    2014-08-15

    Involvement of the cardiovascular system in patients with infectious and parasitic diseases can result from both intrinsic mechanisms of the disease and drug intervention. Malaria is an example, considering that the endothelial injury by Plasmodium-infected erythrocytes can cause circulatory disorders. This is a literature review aimed at discussing the relationship between malaria and endothelial impairment, especially its effects on the cardiovascular system. We discuss the implications of endothelial aggression and the interdisciplinarity that should guide the malaria patient care, whose acute infection can contribute to precipitate or aggravate a preexisting heart disease.

  14. Acute and 28-day repeated oral toxicological evaluation of Kuruthi Azhal Chooranam – a Siddha preparation on rodents

    OpenAIRE

    Marimuthu Kannadasana; Ganesan Sumathy; Palanivel Thirusangu Sangeetha; Chidambaram Saravanababu; Kathirvelu Baskar

    2016-01-01

    Objective: To determine the effect of phytochemicals in acute and repeated dose of 28-day oral toxicity of Kuruthi Azhal Chooranam (KAC) in Sprague Dawley rats of both sexes. Methods: Acute oral toxicity was conducted with 2000 mg/kg body weight of KAC orally and the treated animals were observed for signs of toxicity at 30 min, 1, 2, 4 and 24 h and for up to 14 days. In repeated 28-day oral toxicity study, the KAC formulation was administered orally with 600, 900 and 1200 mg/k...

  15. Acute ghrelin changes food preference from a high-fat diet to chow during binge-like eating in rodents.

    Science.gov (United States)

    Bake, T; Hellgren, K T; Dickson, S L

    2017-04-01

    Ghrelin, an orexigenic hormone released from the empty stomach, provides a gut-brain signal that promotes many appetitive behaviours, including anticipatory and goal-directed behaviours for palatable treats high in sugar and/or fat. In the present study, we aimed to determine whether ghrelin is able to influence and/or may even have a role in binge-like eating behaviour in rodents. Accordingly, we used a palatable scheduled feeding (PSF) paradigm in which ad lib. chow-fed rodents are trained to 'binge' on a high-fat diet (HFD) offered each day for a limited period of 2 hours. After 2 weeks of habituation to this paradigm, on the test day and immediately prior to the 2-hour PSF, rats were administered ghrelin or vehicle solution by the i.c.v. route. Remarkably and unexpectedly, during the palatable scheduled feed, when rats normally only binge on the HFD, those injected with i.c.v. ghrelin started to eat more chow and chow intake remained above baseline for the rest of the 24-hour day. We identify the ventral tegmental area (VTA) (a key brain area involved in food reward) as a substrate involved because these effects could be reproduced, in part, by intra-VTA delivery of ghrelin. Fasting, which increases endogenous ghrelin, immediately prior to a palatable schedule feed also increased chow intake during/after the schedule feed but, in contrast to ghrelin injection, did not reduce HFD intake. Chronic continuous central ghrelin infusion over several weeks enhanced binge-like behaviour in palatable schedule fed rats. Over a 4-week period, GHS-R1A-KO mice were able to adapt and maintain large meals of HFD in a manner similar to wild-type mice, suggesting that ghrelin signalling may not have a critical role in the acquisition or maintenance in this kind of feeding behaviour. In conclusion, ghrelin appears to act as a modulating factor for binge-like eating behaviour by shifting food preference towards a more nutritious choice (from HFD to chow), with these effects

  16. Lipidomics reveals mitochondrial membrane remodeling associated with acute thermoregulation in a rodent with a wide thermoneutral zone.

    Science.gov (United States)

    Pan, Qian; Li, Min; Shi, Yao-Long; Liu, Huwei; Speakman, John R; Wang, De-Hua

    2014-07-01

    Mongolian gerbils (Meriones unguiculatus) have high physiological flexibility in response to acute temperature changes, and have the widest thermoneutral zone (TNZ, 26.5-38.9 °C) reported among small mammals. At the upper critical temperature (T(uc), 38.9 °C), body temperatures of gerbils were significantly increased (39-41 °C) while metabolic rates were maintained at the basal level. In contrast, below the lower critical temperature (T(lc), 26.5 °C), metabolism was elevated and body temperature stable. Rapid changes in mitochondrial membrane lipidome were hypothesized to play an important role during acute thermoregulation of gerbils. Taking advantage of a recent lipidomic technique, we examined changes in the membrane phospholipids environment and free fatty acids (FFA) production in mitochondria between 38 and 27 °C (in the TNZ), and between 27 and 16 °C (below the TNZ). At 38 °C, acute heat stress elicited distinct remodeling in mitochondrial membrane lipidome which related to a potential decrease in mitochondrial respiration and membrane fluidity compared to 27 °C. At 16 °C, a sharply decreased unsaturation index and increased chain lengths were detected in mitochondrial FFA production both in muscle and brown adipose tissue. Our results suggest that mitochondrial membrane lipid remodeling may stabilize membrane function and activity of respiration related membrane protein to maintain a stable metabolic rate at T(uc), and improve heat production by decomposing less fluid fatty acid conjugates of membrane lipids under acute cold exposure. These data therefore imply an important role of membrane remodeling during acute thermoregulation in a non-hibernating endotherm.

  17. Acute and 28-day repeated oral toxicological evaluation of Kuruthi Azhal Chooranam - a Siddha preparation on rodents

    Institute of Scientific and Technical Information of China (English)

    Marimuthu Kannadasana; Ganesan Sumathy; Palanivel Thirusangu Sangeetha; Chidambaram Saravanababu; Kathirvelu Baskar

    2016-01-01

    Objective:To determine the effect of phytochemicals in acute and repeated dose of 28-day oral toxicity of Kuruthi Azhal Chooranam (KAC) in Sprague Dawley rats of both sexes. Methods:Acute oral toxicity was conducted with 2 000 mg/kg body weight of KAC orally and the treated animals were observed for signs of toxicity at 30 min, 1, 2, 4 and 24 h and for up to 14 days. In repeated 28-day oral toxicity study, the KAC formulation was administered orally with 600, 900 and 1 200 mg/kg body weight/day to all the three groups of rats. The animals were observed for clinical signs of toxicity, mortality and morbidity throughout the study. Also body weight, feed consumption, haematological, plasma biochemistry and serum electrolytes, gross pathology, weights of the organ and histology were studied for no-observed-adverse-effect level. High dose of KAC formulation and control reversal groups were also included for delayed toxic effects determination. Results:In the acute toxicity study of KAC formulation, 2 000 mg/kg body weight dose exhibited no toxic signs and mortality during study. In sub-acute 28-day repeated dose toxicity study, there was no significant difference found between control and KAC treated groups (body weight, haematology, biochemistry and serum electrolytes). No abnormalities was found in gross pathology, organs weight and histological observation after KAC treatment. Conclusions:The current study suggests that LD50 of KAC was > 2 000 mg/kg and no-observed-adverse-effect level was>1 200 mg/kg/day in rats. KAC could be used as Siddha drug for various indications.

  18. Intestinal parasites coinfection does not alter plasma cytokines profile elicited in acute malaria in subjects from endemic area of Brazil.

    Science.gov (United States)

    Sánchez-Arcila, Juan Camilo; Perce-da-Silva, Daiana de Souza; Vasconcelos, Mariana Pinheiro Alves; Rodrigues-da-Silva, Rodrigo Nunes; Pereira, Virginia Araujo; Aprígio, Cesarino Junior Lima; Lima, Cleoni Alves Mendes; Fonseca e Fonseca, Bruna de Paula; Banic, Dalma Maria; Lima-Junior, Josué da Costa; Oliveira-Ferreira, Joseli

    2014-01-01

    In Brazil, malaria is prevalent in the Amazon region and these regions coincide with high prevalence of intestinal parasites but few studies explore the interaction between malaria and other parasites. Therefore, the present study evaluates changes in cytokine, chemokine, C-reactive protein, and nitric oxide (NO) concentrations in 264 individuals, comparing plasma from infected individuals with concurrent malaria and intestinal parasites to individuals with either malaria infection alone and uninfected. In the studied population 24% of the individuals were infected with Plasmodium and 18% coinfected with intestinal parasites. Protozoan parasites comprised the bulk of the intestinal parasites infections and subjects infected with intestinal parasites were more likely to have malaria. The use of principal component analysis and cluster analysis associated increased levels of IL-6, TNF-α, IL-10, and CRP and low levels of IL-17A predominantly with individuals with malaria alone and coinfected individuals. In contrast, low levels of almost all inflammatory mediators were associated predominantly with individuals uninfected while increased levels of IL-17A were associated predominantly with individuals with intestinal parasites only. In conclusion, our data suggest that, in our population, the infection with intestinal parasites (mainly protozoan) does not modify the pattern of cytokine production in individuals infected with P. falciparum and P. vivax.

  19. Intestinal Parasites Coinfection Does Not Alter Plasma Cytokines Profile Elicited in Acute Malaria in Subjects from Endemic Area of Brazil

    Directory of Open Access Journals (Sweden)

    Juan Camilo Sánchez-Arcila

    2014-01-01

    Full Text Available In Brazil, malaria is prevalent in the Amazon region and these regions coincide with high prevalence of intestinal parasites but few studies explore the interaction between malaria and other parasites. Therefore, the present study evaluates changes in cytokine, chemokine, C-reactive protein, and nitric oxide (NO concentrations in 264 individuals, comparing plasma from infected individuals with concurrent malaria and intestinal parasites to individuals with either malaria infection alone and uninfected. In the studied population 24% of the individuals were infected with Plasmodium and 18% coinfected with intestinal parasites. Protozoan parasites comprised the bulk of the intestinal parasites infections and subjects infected with intestinal parasites were more likely to have malaria. The use of principal component analysis and cluster analysis associated increased levels of IL-6, TNF-α, IL-10, and CRP and low levels of IL-17A predominantly with individuals with malaria alone and coinfected individuals. In contrast, low levels of almost all inflammatory mediators were associated predominantly with individuals uninfected while increased levels of IL-17A were associated predominantly with individuals with intestinal parasites only. In conclusion, our data suggest that, in our population, the infection with intestinal parasites (mainly protozoan does not modify the pattern of cytokine production in individuals infected with P. falciparum and P. vivax.

  20. Nuclear Factor kB and Inhibitor of kB: Acupuncture Protection Against Acute Focal Cerebral Ischemia in Rodents.

    Science.gov (United States)

    Huang, Wei; Zhou, Zhongyu; Wan, Bijiang; Chen, Guang; Li, Jia

    2017-02-27

    Context • Acute, focal, cerebral ischemic stroke is a leading cause of morbidity and mortality worldwide. Acupuncture is an emerging alternative therapy for treatment of acute brain ischemia. Nevertheless, the precise mechanism underlying the neuroprotective effects of acupuncture has not been elucidated. Nuclear factor κB (NF-κB) and nuclear factor of κ light polypeptide gene enhancer in B cell inhibitor alpha (IκB-α) are involved in cerebral inflammation. However, the involvement of NF-κB and IκB-α in the protective effects of acupuncture on ischemic tolerance remains unknown. Objective • The study evaluated the hypothesis that acupuncture can exert a neuroprotective action in a rat model of middle cerebral artery occlusion (MCAO). Design • The rats were randomly divided into a normal group (N), a sham model group (SM), an MCAO model group (M), a sham acupuncture group (SA), and an acupuncture group (A). Setting • All of processes of this study were conducted at Hubei University of Chinese Medicine (Hubei Shang, China). Animals • The animals were 100 Sprague-Dawley rats, aged 3 mo. Intervention • Craniotomy and electrocoagulation of the middle cerebral artery were conducted to generate acute, focal, cerebral ischemic models in 3 groups, excluding the N and SM groups. The SM group received a surgical fenestration similar to the M group, but the procedure did not include the coagulation of the exposed artery. In the A group, acupuncture was administered at the acupoints Baihui (GV-20) and Renzhong (GV-26). In the SA group, sham acupuncture was performed at a depth of 5 mm at a position close to the left side of the GV-20 and GV-26 points. The N, M, and SM groups received neither the acupuncture nor the sham acupuncture treatment. Outcome Measures • The study (1) evaluated neurological function using the modified neurological severity score; (2) examined the ultrastructure; (3) assessed the infarct volume; (4) determined levels of serum

  1. Cryopreserved, Xeno-Free Human Umbilical Cord Mesenchymal Stromal Cells Reduce Lung Injury Severity and Bacterial Burden in Rodent Escherichia coli-Induced Acute Respiratory Distress Syndrome.

    Science.gov (United States)

    Curley, Gerard F; Jerkic, Mirjana; Dixon, Steve; Hogan, Grace; Masterson, Claire; O'Toole, Daniel; Devaney, James; Laffey, John G

    2017-02-01

    cytokine concentrations, whereas increasing interleukin-10 concentrations. Umbilical cord-mesenchymal stem/stromal cell therapy decreased nicotinamide adenine dinucleotide phosphate-oxidase 2 and inducible nitric oxide synthase and enhanced lung concentrations of superoxide dismutase-2, thereby reducing lung tissue reactive oxidative species concentrations. Our results demonstrate that freshly thawed cryopreserved xeno-free human umbilical cord-mesenchymal stem/stromal cells reduce the severity of rodent E. coli-induced acute respiratory distress syndrome. Umbilical cord-mesenchymal stem/stromal cells, therefore, represent an attractive option for future clinical trials in acute respiratory distress syndrome.

  2. Safety, efficacy and population pharmacokinetics of fixed-dose combination of artesunate-mefloquine in the treatment of acute uncomplicated Plasmodium falciparum malaria in India.

    Science.gov (United States)

    Valecha, Neena; Srivastava, Bina; Dubhashi, N G; Rao, B H Krishnamoorthy; Kumar, Ashwani; Ghosh, S K; Singh, Jai Prakash Narayan; Kiechel, J R; Sharma, Bhawna; Jullien, V; Dash, A P; Taylor, W R J; Anvikar, Anupkumar R

    2013-12-01

    India has switched over to artemisinin-based combination therapy (ACT) for the treatment of acute uncomplicated Plasmodium falciparum malaria and the ACT used in the national programme is artesunate + sulphadoxine-pyrimethamine. Since the efficacy of ACT is dependent also on the partner drug, there is a need to evaluate and deploy multiple ACTs. This multicentre, single-arm, open-label clinical trial was carried out to assess the efficacy, safety and population pharmacokinetics of a fixed dose combination (FDC) artesunate mefloquine (ASMQ) in P. falciparum infected, Indian adults at Panjim, Goa, and Mangalore, Karnataka between December 2007 and November 2008. A total of 77 patients (males 74) were screened and enrolled: 42 at Goa and 35 at Mangalore with a median age of 25 yr (range 18-55 yr). One patient failed in treatment on D53, a PCR proven new infection, seven developed recurrent vivax parasitaemia and 11 did not have a parasitological endpoint. By per protocol analysis, the D63 cure rate was 58/59 (98.3; 95% C.I. 90.9-99.9%), and 58/58, with PCR correction. ASMQ was well-tolerated and no serious adverse events were reported. The study showed that the ASMQ FDC was efficacious and well-tolerated for the treatment of acute, uncomplicated P. falciparum malaria in highly endemic, chloroquine resistant areas of Goa and Mangalore. It is a viable option for India.

  3. Increased plasma levels of soluble ICAM-1 and ELAM-1 (E-selectin) during acute Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Hviid, L; Theander, T G; Elhassan, I M

    1993-01-01

    Acute P. falciparum malaria is associated with a loss of antigen-responsiveness of peripheral T cells, depletion of T cells characterized by high surface expression of the adhesion molecule LFA-1, and increased plasma levels of the T-cell activation marker soluble IL-2 receptor (sIL-2R). In the p......Acute P. falciparum malaria is associated with a loss of antigen-responsiveness of peripheral T cells, depletion of T cells characterized by high surface expression of the adhesion molecule LFA-1, and increased plasma levels of the T-cell activation marker soluble IL-2 receptor (sIL-2R...... significantly correlated, and were furthermore associated with a concomitant increase in plasma levels of sIL-2R. Finally, plasma levels of sICAM-1, but not sELAM-1, were inversely correlated to the fraction of peripheral T cells having high surface expression of LFA-1, the receptor for T-cell adhesion to ICAM...

  4. Post-Plasmodium vivax malaria cerebellar ataxia and optic neuritis: A new form of delayed cerebellar ataxia or cerebellar variant of acute disseminated encephalomyelitis?

    Directory of Open Access Journals (Sweden)

    Gaurav M Kasundra

    2015-01-01

    Full Text Available Acute disseminated encephalomyelitis (ADEM is commonly seen after viral and bacterial infections, immunization, and Plasmodium falciparum (PF malaria. Plasmodium vivax (PV rarely causes ADEM. We report a 14-year-old female patient who presented with acute onset bilateral cerebellar ataxia and optic neuritis, 2 weeks after recovery from PV. Magnetic resonance imaging showed bilateral cerebellar hyperintensities suggestive of ADEM. No specific viral etiology was found on cerebrospinal fluid examination. Patient responded well to treatment without any sequelae. Thus, PV too is an important cause of ADEM along with PF. Two of the previously reported cases had co-infection with falciparum malaria. The only other two reported cases, as also this patient, are from Asia. A geographical or racial predisposition needs to be evaluated. Also, a possibility of post-PV delayed cerebellar ataxia, which is classically described post-PF infection, may be considered as it may be clinically, radiologically, and prognostically indistinguishable from a milder presentation of ADEM.

  5. Anti-Inflammatory Effect of Emblica officinalis in Rodent Models of Acute and Chronic Inflammation: Involvement of Possible Mechanisms

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    Mahaveer Golechha

    2014-01-01

    Full Text Available Emblica officinalis, commonly known as amla in Ayurveda, is unarguably the most important medicinal plant for prevention and treatment of various ailments. The present study investigated the anti-inflammatory activity of hydroalcoholic extract of Emblica officinalis (HAEEO. Acute inflammation in rats was induced by the subplantar injection of carrageenan, histamine, serotonin, and prostaglandin E2 and chronic inflammation was induced by the cotton pellet granuloma. Intraperitoneal (i.p. administration of HAEEO at all the tested doses (300, 500, and 700 mg/kg significantly (P<0.001 inhibited rat paw edema against all phlogistic agents and also reduced granuloma formation. However, at the dose of 700 mg/kg, HAEEO exhibited maximum anti-inflammatory activity in all experimental models, and the effects were comparable to that of the standard anti-inflammatory drugs. Additionally, in paw tissue the antioxidant activity of HAEEO was also measured and it was found that HAEEO significantly (P<0.001 increased glutathione, superoxide dismutase, and catalase activity and subsequently reduced lipid peroxidation evidenced by reduced malondialdehyde. Taken all together, the results indicated that HAEEO possessed potent anti-inflammatory activity and it may hold therapeutic promise in the management of acute and chronic inflammatory conditions.

  6. Evaluation of Mitochondrial Function in the CNS of Rodent Models of Alzheimer's Disease - High Resolution Respirometry Applied to Acute Hippocampal Slices.

    Science.gov (United States)

    Dias, Candida; Barbosa, Rui M; Laranjinha, Joao; Ledo, Ana

    2014-10-01

    Alzheimer's disease (AD) is a multifactorial disease characterized by extracellular deposits of amyloid plaques and intracellular neurofibrillary tangles. These hallmark alterations are preceded by synaptic deterioration, changes in neuromolecular plasticity phenomena, mitochondrial dysfunction, increase in oxidative damage to cellular constituents and decreased energy metabolism. The hippocampus is a structure of the temporal medial lobe implicated in specific forms of memory processes. It is also one of the first and most affected regions of the CNS in AD. Here we present a novel approach to the study if mitochondrial function/disfunction in 2 rodent models of AD: an acute rat model obtained by intracerebroventricular injection of the toxin streptozotocin (STZ) and a progressive triple transgenic mouse model (3TgAD) harboring PS1M146V, APPSwe, and tauP301L transgenes. Mitochondrial dysfunction has classically been assessed in such models by isolating mitochondria, synaptossoms or working with cell cultures. Anyone of these approaches destroys the intricate intercellular connectivity and cytoarchitecture of neuronal tissue. We used acute hippocampal slices obtained from the 2 models of AD and evaluated changes in mitochondrial function as a function of disease and/or age. Mitochondrial stress test were performed on the high resolution respirometry (Oroboros 2K Oxymeter). Upon analysis of oxygen consumption rates (OCR) we observed significant decreases in basal OCR, maximal respiratory capacity, ATP turnover and a tendency for decrease in sparing capacity in the STZ rat model compared to shame injected animals. Regarding the 3TgAD model we observed an age-dependent decrease in all parameters evaluated in the mitochondrial stress test, in both 3TgAD and NTg animals. However, although a tendency towards decreased OCR was observed when comparing 3TgAD and age-matched NTg animals, no statistically significant difference was observed. Copyright © 2014. Published by

  7. A Herbal Composition of Semen Hoveniae, Radix Puerariae, and Fructus Schisandrae Shows Potent Protective Effects on Acute Alcoholic Intoxication in Rodent Models

    Directory of Open Access Journals (Sweden)

    Jie Xiong

    2012-01-01

    Full Text Available This study is designed to evaluate the effects of a herbal composition of Semen Hoveniae, Radix Puerariae and Fructus Schisandrae (SRF against acute alcoholic intoxication. The animals were treated with SRF extract (SRFE for 14 days, and ethanol was conducted subsequent to the final treatment. The effects of SRFE on righting reflex, inebriety rates, kinetic parameters of blood ethanol and acetaldehyde were determined. In addition; levels of alcohol dehydrogenase (ADH and aldehyde dehydrogenase (ALDH, the activities of cytochrome P450 2E1 (CYP2E1, selected antioxidative enzymes, and the contents of malonaldehyde (MDA were measured. SRFE-pretreated rodents exhibited lower rates of intoxication, longer times to loss of righting reflex, and shortened times to recovery of righting reflex than in controls. The peak concentrations and area under the time-concentration curves were lower in the pretreated animals than in controls, which corresponded to higher levels of ADH and ALDH in both gastrointestines and livers of the SRFE-treated animals. The activities of CYP2E1 were lower in SRFE-pretreated animals, which also exhibited higher activities of some antioxidant enzymes and lower hepatic MDA levels. These findings suggest that the anti-inebriation effects of SRFE may involve inhibition of ethanol absorption, promotion of ethanol metabolism, and enhancing hepatic anti-oxidative functions.

  8. Redox status of acute pancreatitis as measured by cyclic voltammetry: initial rodent studies to assess disease severity.

    Science.gov (United States)

    Mittal, Anubhav; Flint, Richard J; Fanous, Medhat; Delahunt, Brett; Kilmartin, Paul A; Cooper, Garth J S; Windsor, John A; Phillips, Anthony R J

    2008-03-01

    To determine whether serum antioxidant capacity as measured by the electrochemical technique cyclic voltammetry could be used to resolve differences in the severity of an inflammatory disease such as acute pancreatitis. Experimental animal study. Animal laboratory, Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, New Zealand. Male Wistar rats. A total of 48 inbred male Wistar rats were studied in five experimental groups. Group 1 (baseline reference, immediate euthanasia, n = 14) had no surgical intervention. Group 2 (sham, n = 9) had identical surgical procedures to the pancreatitis groups except for the intraductal infusion. Groups 3-5 (n = 9, n = 10, and n = 6, respectively) had acute pancreatitis induced by the pancreatic intraductal infusion of 3%, 4%, or 5% sodium taurocholate, respectively. Groups 2-5 were killed after 12 hrs. Cyclic voltammetry involves scanning the voltage of a working electrode while recording the anodic current produced as the low molecular weight antioxidants in the solution are oxidized on the surface of the working electrode. The current produced is proportional to the combined concentration of the antioxidants. There was a significant positive correlation of the first cyclic voltammetric peak maximum with pancreatic histologic severity (Spearman's r = .51, p = .007) and with a number of other markers of systemic severity, notably bicarbonate (r = -.57, p = .002), base excess (r = -.65, p cyclic voltammetric peak maximum was superior at indicating the severity of the disease state compared with a standard method of total antioxidant capacity measurement. In experimental pancreatitis, the first cyclic voltammetric peak maximum showed significant correlations with histologic and systemic indices of severity. Further clinical studies are now needed to define the role of cyclic voltammetry in monitoring the progression of this and other severe illness in the critical care setting.

  9. Safety of a single low-dose of primaquine in addition to standard artemether-lumefantrine regimen for treatment of acute uncomplicated Plasmodium falciparum malaria in Tanzania.

    Science.gov (United States)

    Mwaiswelo, Richard; Ngasala, Billy E; Jovel, Irina; Gosling, Roland; Premji, Zul; Poirot, Eugenie; Mmbando, Bruno P; Björkman, Anders; Mårtensson, Andreas

    2016-06-10

    This study assessed the safety of the new World Health Organization (WHO) recommendation of adding a single low-dose of primaquine (PQ) to standard artemisinin-based combination therapy (ACT), regardless of individual glucose-6-phosphate dehydrogenase (G6PD) status, for treatment of acute uncomplicated Plasmodium falciparum malaria in Tanzania. Men and non-pregnant, non-lactating women aged ≥1 year with uncomplicated P. falciparum malaria were enrolled and randomized to either standard artemether-lumefantrine (AL) regimen alone or with a 0.25 mg/kg single-dose of PQ. PQ was administered concomitantly with the first AL dose. All drug doses were supervised. Safety was evaluated between days 0 and 28. G6PD status was assessed using rapid test (CareStart™) and molecular genotyping. The primary endpoint was mean percentage relative reduction in haemoglobin (Hb) concentration (g/dL) between days 0 and 7 by genotypic G6PD status and treatment arm. Overall, 220 patients, 110 per treatment arm, were enrolled, of whom 33/217 (15.2 %) were phenotypically G6PD deficient, whereas 15/110 (13.6 %) were genotypically hemizygous males, 5/110 (4.5 %) homozygous females and 22/110 (20 %) heterozygous females. Compared to genotypically G6PD wild-type/normal [6.8, 95 % confidence interval (CI) 4.67-8.96], only heterozygous patients in AL arm had significant reduction in day-7 mean relative Hb concentration (14.3, 95 % CI 7.02-21.55, p=0.045), however, none fulfilled the pre-defined haemolytic threshold value of ≥25 % Hb reduction. After adjustment for baseline parasitaemia, Hb, age and sex the mean relative Hb reduction was not statistically significant in both heterozygous and hemizygous/homozygous patients in both arms. A majority of the adverse events (AEs) were mild and unrelated to the study drugs. However, six (4.4 %) episodes, three per treatment arm, of acute haemolytic anaemia occurred between days 0 and 7. Three occurred in phenotypically G6PD deficient

  10. Chemotherapy of Rodent Malaria. Part 1

    Science.gov (United States)

    1987-10-01

    A.stephensi. (X 26,000) 95 During the course of routine EM screening of our colony of A.stephensi for the presence of pathogenic micro-organisms such as...Warhurst, D.C. Antimalarial activity of Ailanthus altissima stem. In: Phytochemical Society of Europe Symposium on biologically active natural

  11. Malaria cerebral Cerebral malaria

    OpenAIRE

    Carlos Hugo Zapata Zapata; Silvia Blair Trujillo

    2003-01-01

    La malaria Cerebral (MC) es la complicación más frecuente de la malaria por P. falciparum; aproximadamente el 90% de las personas que la han padecido se recuperan completamente sin secuelas neurológicas. Aún no se conoce con claridad su patogénesis pero se han postulado cuatro hipótesis o mecanismos posibles: 1) citoadherencia y secuestro de glóbulos rojos parasitados en la microvasculatura cerebral; 2) formación de rosetas y aglutinación de glóbulos rojos parasitados; 3) producción de citoqu...

  12. Dibucaine mitigates spreading depolarization in human neocortical slices and prevents acute dendritic injury in the ischemic rodent neocortex.

    Directory of Open Access Journals (Sweden)

    W Christopher Risher

    Full Text Available Spreading depolarizations that occur in patients with malignant stroke, subarachnoid/intracranial hemorrhage, and traumatic brain injury are known to facilitate neuronal damage in metabolically compromised brain tissue. The dramatic failure of brain ion homeostasis caused by propagating spreading depolarizations results in neuronal and astroglial swelling. In essence, swelling is the initial response and a sign of the acute neuronal injury that follows if energy deprivation is maintained. Choosing spreading depolarizations as a target for therapeutic intervention, we have used human brain slices and in vivo real-time two-photon laser scanning microscopy in the mouse neocortex to study potentially useful therapeutics against spreading depolarization-induced injury.We have shown that anoxic or terminal depolarization, a spreading depolarization wave ignited in the ischemic core where neurons cannot repolarize, can be evoked in human slices from pediatric brains during simulated ischemia induced by oxygen/glucose deprivation or by exposure to ouabain. Changes in light transmittance (LT tracked terminal depolarization in time and space. Though spreading depolarizations are notoriously difficult to block, terminal depolarization onset was delayed by dibucaine, a local amide anesthetic and sodium channel blocker. Remarkably, the occurrence of ouabain-induced terminal depolarization was delayed at a concentration of 1 µM that preserves synaptic function. Moreover, in vivo two-photon imaging in the penumbra revealed that, though spreading depolarizations did still occur, spreading depolarization-induced dendritic injury was inhibited by dibucaine administered intravenously at 2.5 mg/kg in a mouse stroke model.Dibucaine mitigated the effects of spreading depolarization at a concentration that could be well-tolerated therapeutically. Hence, dibucaine is a promising candidate to protect the brain from ischemic injury with an approach that does not rely on

  13. Aging potentiates the acute and chronic neurological symptoms of pyrithiamine-induced thiamine deficiency in the rodent.

    Science.gov (United States)

    Pitkin, S R; Savage, L M

    2001-03-15

    The present study aimed to assess the role of advanced age in the development and manifestation of thiamine deficiency using an animal model of Wernicke-Korsakoff syndrome (WKS). Interactions between pyrithiamine-induced thiamine deficiency (PTD) and age were examined relative to working memory impairment and neuropathology in Fischer 344 rats. Young (2-3 months) and aged (22-23 months) F344 rats were assigned to one of two treatment conditions: PTD or pair-fed control (PF). Rats in the former group were further divided into three groups according to duration of PTD treatment. Working memory was assessed with an operant matching-to-position (MTP) task; after testing, animals were sacrificed and both gross and immunocytochemical measures of brain pathology were obtained. Aged rats exhibited acute neurological disturbances during the PTD treatment regime earlier than did young rats, and also developed more extensive neuropathology with a shorter duration of PTD. Aged rats displayed increased brain shrinkage (smaller frontal cortical and callosal thickness) as well as enhanced astrocytic activity in the thalamus and a decrease in ChAT-positive cell numbers in the medial septum; the latter two measures of neuropathology were potentiated by PTD. In both young and aged rats, and to a greater degree in the latter group, PTD reduced thalamic volume. Behaviorally, aged rats displayed impaired choice accuracy on the delayed MTP task. Regardless of age, rats with lesions centered on the internal medullary lamina of the thalamus also displayed impaired choice accuracy. Moreover, increased PTD treatment duration led to increased response times on the delayed MTP task. These results suggest that aging does indeed potentiate the neuropathology associated with experimental thiamine deficiency, supporting an age coupling hypothesis of alcohol-related neurological disorders.

  14. Serum levels of soluble urokinase plasminogen activator receptor is associated with parasitemia in children with acute Plasmodium falciparum malaria infection

    DEFF Research Database (Denmark)

    Perch, M; Kofoed, Pe; Fischer, Torge

    2004-01-01

    days after treatment. Children younger than 6 years who presented with fever or other symptoms compatible with malaria were enrolled. Blood films and samples were collected on day 0 and day 7. Twenty-five children were allocated to each of three groups according to the amount of Plasmodium falciparum...

  15. Plasmodium vivax malaria: An unusual presentation

    Directory of Open Access Journals (Sweden)

    Kasliwal Prasad

    2009-01-01

    Full Text Available Acute renal failure, disseminated intravascular coagulation (DIC, acute respiratory distress syndrome (ARDS, hypoglycemia, coma, or epileptic seizures are manifestations of severe Plasmodium falciparum malaria. On the other hand, Plasmodium vivax malaria seldom results in pulmonary damage, and pulmonary complications are exceedingly rare. We report the case of a 42-year-old male living in a malaria-endemic area who presented with ARDS and was diagnosed as having Plasmodium vivax malaria. A diagnosis of Plasmodium vivax malaria was established by a positive Plasmodium LDH immunochromatographic assay while a negative PfHRP2 based assay ruled out P. falciparum malaria. After specific anti-plasmodial therapy and intensive supportive care, the patient recovered and was discharged from hospital. The use of NIPPV in vivax-malaria related ARDS was associated with a good outcome.

  16. Artesunate-mefloquine combination therapy in acute Plasmodium falciparum malaria in young children: a field study regarding neurological and neuropsychiatric safety

    Directory of Open Access Journals (Sweden)

    Hatz Christoph

    2010-10-01

    Full Text Available Abstract Background Mefloquine-artesunate combination therapy for uncomplicated falciparum malaria is one of the treatments used in African children. Data concerning neurological safety in adults and children treated with mefloquine and artesunate combination therapy is well documented in Asia. Safety data for neurological and neuropsychiatric side effects of mefloquine and artesunate combination therapy in African children are scarce, although WHO recommends this therapy in Africa. Methods A phase IV, open label, single arm study was conducted among African children between 10 and 20 kg with acute uncomplicated falciparum malaria. They were treated over three consecutive days with a paediatric fixed-dose combination of artesunate (50 mg/d and mefloquine (125 mg/d. Parasitological, clinical and neurological examinations and standardized questions about neuropsychiatric symptoms were carried out on days 0, 4, 7, 28 and 63. The primary objective was to assess the neurological and neuropsychiatric safety of artesunate-mefloquine combination therapy in young children. Results From December 2007 to March 2009, 220 children with uncomplicated Plasmodium falciparum malaria were treated with artesunate and mefloquine. 213 children were analysed according to study protocol. 50 neurological and neuropsychiatric adverse events occurred in 28 patients. Eleven drug-related neurological and neuropsychiatric adverse events occurred in eight patients. Sleeping disorders were present in 2.3%, neurological disorders in 1.4%, neuropsychiatric disorders in 1% and eating disorders in 0.5% of the patients. Adverse events were of mild to moderate intensity and resolved spontaneously. Conclusion African children showed a low percentage of self-limited neurological and neuropsychiatric adverse events, confirming studies on neurological safety in Asian children treated with artesunate and mefloquine. Sleeping disorders were most frequently observed.

  17. Vagal nerve stimulation blocks interleukin 6-dependent synaptic hyperexcitability induced by lipopolysaccharide-induced acute stress in the rodent prefrontal cortex.

    Science.gov (United States)

    Garcia-Oscos, Francisco; Peña, David; Housini, Mohammad; Cheng, Derek; Lopez, Diego; Borland, Michael S; Salgado-Delgado, Roberto; Salgado, Humberto; D'Mello, Santosh; Kilgard, Michael P; Rose-John, Stefan; Atzori, Marco

    2015-01-01

    The ratio between synaptic inhibition and excitation (sI/E) is a critical factor in the pathophysiology of neuropsychiatric disease. We recently described a stress-induced interleukin-6 dependent mechanism leading to a decrease in sI/E in the rodent temporal cortex. The aim of the present study was to determine whether a similar mechanism takes place in the prefrontal cortex, and to elaborate strategies to prevent or attenuate it. We used aseptic inflammation (single acute injections of lipopolysaccharide, LPS, 10mg/kg) as stress model, and patch-clamp recording on a prefrontal cortical slice preparation from wild-type rat and mice, as well as from transgenic mice in which the inhibitor of IL-6 trans-signaling sgp130Fc was produced in a brain-specific fashion (sgp130Fc mice). The anti-inflammatory reflex was activated either by vagal nerve stimulation or peripheral administration of the nicotinic α7 receptor agonist PHA543613. We found that the IL-6-dependent reduction in prefrontal cortex synaptic inhibition was blocked in sgp130Fc mice, or - in wild-type animals - upon application sgp130Fc. Similar results were obtained by activating the "anti-inflammatory reflex" - a neural circuit regulating peripheral immune response - by stimulation of the vagal nerve or through peripheral administration of the α7 nicotinic receptor agonist PHA543613. Our results indicate that the prefrontal cortex is an important potential target of IL-6 mediated trans-signaling, and suggest a potential new avenue in the treatment of a large class of hyperexcitable neuropsychiatric conditions, including epilepsy, schizophrenic psychoses, anxiety disorders, autism spectrum disorders, and depression.

  18. Big bang in the evolution of extant malaria parasites.

    Science.gov (United States)

    Hayakawa, Toshiyuki; Culleton, Richard; Otani, Hiroto; Horii, Toshihiro; Tanabe, Kazuyuki

    2008-10-01

    Malaria parasites (genus Plasmodium) infect all classes of terrestrial vertebrates and display host specificity in their infections. It is therefore assumed that malaria parasites coevolved intimately with their hosts. Here, we propose a novel scenario of malaria parasite-host coevolution. 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.

  19. In vivo approaches reveal a key role for DCs in CD4+ T cell activation and parasite clearance during the acute phase of experimental blood-stage malaria.

    Directory of Open Access Journals (Sweden)

    Henrique Borges da Silva

    2015-02-01

    Full Text Available Dendritic cells (DCs are phagocytes that are highly specialized for antigen presentation. Heterogeneous populations of macrophages and DCs form a phagocyte network inside the red pulp (RP of the spleen, which is a major site for the control of blood-borne infections such as malaria. However, the dynamics of splenic DCs during Plasmodium infections are poorly understood, limiting our knowledge regarding their protective role in malaria. Here, we used in vivo experimental approaches that enabled us to deplete or visualize DCs in order to clarify these issues. To elucidate the roles of DCs and marginal zone macrophages in the protection against blood-stage malaria, we infected DTx (diphtheria toxin-treated C57BL/6.CD11c-DTR mice, as well as C57BL/6 mice treated with low doses of clodronate liposomes (ClLip, with Plasmodium chabaudi AS (Pc parasites. The first evidence suggesting that DCs could contribute directly to parasite clearance was an early effect of the DTx treatment, but not of the ClLip treatment, in parasitemia control. DCs were also required for CD4+ T cell responses during infection. The phagocytosis of infected red blood cells (iRBCs by splenic DCs was analyzed by confocal intravital microscopy, as well as by flow cytometry and immunofluorescence, at three distinct phases of Pc malaria: at the first encounter, at pre-crisis concomitant with parasitemia growth and at crisis when the parasitemia decline coincides with spleen closure. In vivo and ex vivo imaging of the spleen revealed that DCs actively phagocytize iRBCs and interact with CD4+ T cells both in T cell-rich areas and in the RP. Subcapsular RP DCs were highly efficient in the recognition and capture of iRBCs during pre-crisis, while complete DC maturation was only achieved during crisis. These findings indicate that, beyond their classical role in antigen presentation, DCs also contribute to the direct elimination of iRBCs during acute Plasmodium infection.

  20. Pyronaridine-artesunate versus chloroquine in patients with acute Plasmodium vivax malaria: a randomized, double-blind, non-inferiority trial.

    Directory of Open Access Journals (Sweden)

    Yi Poravuth

    in acute uncomplicated P. vivax malaria was at least that of chloroquine. As pyronaridine-artesunate is also efficacious against P. falciparum malaria, this combination has potential utility as a global antimalarial drug. TRIAL REGISTRATION: Clinicaltrials.gov NCT00440999.

  1. Pyronaridine-Artesunate versus Chloroquine in Patients with Acute Plasmodium vivax Malaria: A Randomized, Double-Blind, Non-Inferiority Trial

    Science.gov (United States)

    Poravuth, Yi; Socheat, Duong; Rueangweerayut, Ronnatrai; Uthaisin, Chirapong; Pyae Phyo, Aung; Valecha, Neena; Rao, B. H. Krishnamoorthy; Tjitra, Emiliana; Purnama, Asep; Borghini-Fuhrer, Isabelle; Duparc, Stephan; Shin, Chang-Sik; Fleckenstein, Lawrence

    2011-01-01

    Background New antimalarials are needed for P. vivax and P. falciparum malaria. This study compared the efficacy and safety of pyronaridine-artesunate with that of chloroquine for the treatment of uncomplicated P. vivax malaria. Methods and Findings This phase III randomized, double-blind, non-inferiority trial included five centers across Cambodia, Thailand, India, and Indonesia. In a double-dummy design, patients (aged >3–≤60 years) with microscopically confirmed P. vivax mono-infection were randomized (1∶1) to receive pyronaridine-artesunate (target dose 7.2∶2.4 mg/kg to 13.8∶4.6 mg/kg) or chloroquine (standard dose) once daily for three days. Each treatment group included 228 randomized patients. Outcomes for the primary endpoint, Day-14 cure rate in the per-protocol population, were 99.5%, (217/218; 95%CI 97.5, 100) with pyronaridine-artesunate and 100% (209/209; 95%CI 98.3, 100) with chloroquine. Pyronaridine was non-inferior to chloroquine: treatment difference −0.5% (95%CI −2.6, 1.4), i.e., the lower limit of the 2-sided 95%CI for the treatment difference was greater than −10%. Pyronaridine-artesunate cure rates were non-inferior to chloroquine for Days 21, 28, 35 and 42. Parasite clearance time was shorter with pyronaridine-artesunate (median 23.0 h) versus chloroquine (32.0 h; pestimates of post-baseline P. falciparum infection incidence until Day 42 were 2.5% with pyronaridine-artesunate, 6.1% with chloroquine (p = 0.048, log-rank test). Post-baseline P. vivax or P. falciparum infection incidence until Day 42 was 6.8% and 12.4%, respectively (p = 0.022, log rank test). There were no deaths. Adverse events occurred in 92/228 (40.4%) patients with pyronaridine-artesunate and 72/228 (31.6%) with chloroquine. Mild and transient increases in hepatic enzymes were observed for pyronaridine-artesunate. Conclusion Pyronaridine-artesunate efficacy in acute uncomplicated P. vivax malaria was at least that of chloroquine. As pyronaridine

  2. In Vivo Approaches Reveal a Key Role for DCs in CD4+ T Cell Activation and Parasite Clearance during the Acute Phase of Experimental Blood-Stage Malaria

    Science.gov (United States)

    Borges da Silva, Henrique; Fonseca, Raíssa; Cassado, Alexandra dos Anjos; Machado de Salles, Érika; de Menezes, Maria Nogueira; Langhorne, Jean; Perez, Katia Regina; Cuccovia, Iolanda Midea; Ryffel, Bernhard; Barreto, Vasco M.; Marinho, Cláudio Romero Farias; Boscardin, Silvia Beatriz; Álvarez, José Maria; D’Império-Lima, Maria Regina; Tadokoro, Carlos Eduardo

    2015-01-01

    Dendritic cells (DCs) are phagocytes that are highly specialized for antigen presentation. Heterogeneous populations of macrophages and DCs form a phagocyte network inside the red pulp (RP) of the spleen, which is a major site for the control of blood-borne infections such as malaria. However, the dynamics of splenic DCs during Plasmodium infections are poorly understood, limiting our knowledge regarding their protective role in malaria. Here, we used in vivo experimental approaches that enabled us to deplete or visualize DCs in order to clarify these issues. To elucidate the roles of DCs and marginal zone macrophages in the protection against blood-stage malaria, we infected DTx (diphtheria toxin)-treated C57BL/6.CD11c-DTR mice, as well as C57BL/6 mice treated with low doses of clodronate liposomes (ClLip), with Plasmodium chabaudi AS (Pc) parasites. The first evidence suggesting that DCs could contribute directly to parasite clearance was an early effect of the DTx treatment, but not of the ClLip treatment, in parasitemia control. DCs were also required for CD4+ T cell responses during infection. The phagocytosis of infected red blood cells (iRBCs) by splenic DCs was analyzed by confocal intravital microscopy, as well as by flow cytometry and immunofluorescence, at three distinct phases of Pc malaria: at the first encounter, at pre-crisis concomitant with parasitemia growth and at crisis when the parasitemia decline coincides with spleen closure. In vivo and ex vivo imaging of the spleen revealed that DCs actively phagocytize iRBCs and interact with CD4+ T cells both in T cell-rich areas and in the RP. Subcapsular RP DCs were highly efficient in the recognition and capture of iRBCs during pre-crisis, while complete DC maturation was only achieved during crisis. These findings indicate that, beyond their classical role in antigen presentation, DCs also contribute to the direct elimination of iRBCs during acute Plasmodium infection. PMID:25658925

  3. Cerebral malaria Malaria cerebral

    OpenAIRE

    Silvia Blair Trujillo; Carlos Hugo Zapata Zapata

    2003-01-01

    Is the most common complication of P. falciparum malaria; nearly 90% of people who have suffered CM can recover without neurological problems. Currently there are four hypotheses that explain pathogenesis of CM: cytoadherence and sequestering of parasitized red blood cells to cerebral capillaries; rosette formation and parasitized red blood cells agglutination; production of cytokines and activation of second messengers and opening of the blood-brain barrier. However the main question remains...

  4. Malaria (For Parents)

    Science.gov (United States)

    ... Old Feeding Your 1- to 2-Year-Old Malaria KidsHealth > For Parents > Malaria A A A What's ... Prevention Diagnosis and Treatment en español Malaria About Malaria Malaria is a common infection in hot, tropical ...

  5. Plasmodium vivax hospitalizations in a monoendemic malaria region: severe vivax malaria?

    Science.gov (United States)

    Quispe, Antonio M; Pozo, Edwar; Guerrero, Edith; Durand, Salomón; Baldeviano, G Christian; Edgel, Kimberly A; Graf, Paul C F; Lescano, Andres G

    2014-07-01

    Severe malaria caused by Plasmodium vivax is no longer considered rare. To describe its clinical features, we performed a retrospective case control study in the subregion of Luciano Castillo Colonna, Piura, Peru, an area with nearly exclusive vivax malaria transmission. Severe cases and the subset of critically ill cases were compared with a random set of uncomplicated malaria cases (1:4). Between 2008 and 2009, 6,502 malaria cases were reported, including 106 hospitalized cases, 81 of which fit the World Health Organization definition for severe malaria. Of these 81 individuals, 28 individuals were critically ill (0.4%, 95% confidence interval = 0.2-0.6%) with severe anemia (57%), shock (25%), lung injury (21%), acute renal failure (14%), or cerebral malaria (11%). Two potentially malaria-related deaths occurred. Compared with uncomplicated cases, individuals critically ill were older (38 versus 26 years old, P malaria monoinfection with critical illness is more common than previously thought.

  6. Glucocorticosteroids in nano-sterically stabilized liposomes are efficacious for elimination of the acute symptoms of experimental cerebral malaria.

    Science.gov (United States)

    Waknine-Grinberg, Judith H; Even-Chen, Simcha; Avichzer, Jasmine; Turjeman, Keren; Bentura-Marciano, Annael; Haynes, Richard K; Weiss, Lola; Allon, Nahum; Ovadia, Haim; Golenser, Jacob; Barenholz, Yechezkel

    2013-01-01

    Cerebral malaria is the most severe complication of Plasmodium falciparum infection, and a leading cause of death in children under the age of five in malaria-endemic areas. We report high therapeutic efficacy of a novel formulation of liposome-encapsulated water-soluble glucocorticoid prodrugs, and in particular β-methasone hemisuccinate (BMS), for treatment of experimental cerebral malaria (ECM), using the murine P. berghei ANKA model. BMS is a novel derivative of the potent steroid β-methasone, and was specially synthesized to enable remote loading into nano-sterically stabilized liposomes (nSSL), to form nSSL-BMS. The novel nano-drug, composed of nSSL remote loaded with BMS, dramatically improves drug efficacy and abolishes the high toxicity seen upon administration of free BMS. nSSL-BMS reduces ECM rates in a dose-dependent manner and creates a survival time-window, enabling administration of an antiplasmodial drug, such as artemisone. Administration of artemisone after treatment with the nSSL-BMS results in complete cure. Treatment with BMS leads to lower levels of cerebral inflammation, demonstrated by changes in cytokines, chemokines, and cell markers, as well as diminished hemorrhage and edema, correlating with reduced clinical score. Administration of the liposomal formulation results in accumulation of BMS in the brains of sick mice but not of healthy mice. This steroidal nano-drug effectively eliminates the adverse effects of the cerebral syndrome even when the treatment is started at late stages of disease, in which disruption of the blood-brain barrier has occurred and mice show clear signs of neurological impairment. Overall, sequential treatment with nSSL-BMS and artemisone may be an efficacious and well-tolerated therapy for prevention of CM, elimination of parasites, and prevention of long-term cognitive damage.

  7. UK malaria treatment guidelines.

    Science.gov (United States)

    Lalloo, David G; Shingadia, Delane; Pasvol, Geoffrey; Chiodini, Peter L; Whitty, Christopher J; Beeching, Nicholas J; Hill, David R; Warrell, David A; Bannister, Barbara A

    2007-02-01

    ); quinine is highly effective but poorly tolerated in prolonged dosage and is always supplemented by additional treatment, usually with oral doxycycline. ALL patients treated for P. falciparum malaria should be admitted to hospital for at least 24 h, since patients can deteriorate suddenly, especially early in the course of treatment. Severe falciparum malaria, or infections complicated by a relatively high parasite count (more than 2% of red blood cells parasitized), should be treated with intravenous therapy until the patient is well enough to continue with oral treatment. In the UK, the treatment of choice for severe or complicated malaria is currently an infusion of intravenous quinine. This may exacerbate hypoglycaemia that can occur in malaria; patients treated with intravenous quinine therefore require careful monitoring. Intravenous artesunate reduces high parasite loads more rapidly than quinine and is more effective in treating severe malaria in selected situations. It can also be used in patients with contra-indications to quinine. Intravenous artesunate is unlicensed in the EU. Assistance in obtaining artesunate may be sought from specialist tropical medicine centres, on consultation, for named patients. Patients with severe or complicated malaria should be managed in a high dependency or intensive care environment. They may require haemodynamic support and management of acute respiratory distress syndrome, disseminated intravascular coagulation, renal impairment/failure, seizures, and severe intercurrent infections including gram-negative bacteraemia/septicaemia. Falciparum malaria in pregnancy is more likely to be severe and complicated: the placenta contains high levels of parasites. Stillbirth or early delivery may occur and diagnosis can be difficult if parasites are concentrated in the placenta and scanty in the blood. The treatment of choice for falciparum malaria in pregnancy is quinine; doxycycline is contraindicated in pregnancy but clindamycin can be

  8. Effects of pyrimethamine-sulphadoxine, chloroquine plus chlorpheniramine, and amodiaquine plus pyrimethamine-sulphadoxine on gametocytes during and after treatment of acute, uncomplicated malaria in children

    Directory of Open Access Journals (Sweden)

    A Sowunmi

    2006-12-01

    Full Text Available The effects of pyrimethamine-sulphadoxine (PS, chloroquine plus chlorpheniramine, a H1 receptor antagonist that reverses chloroquine resistance in Plasmodium falciparum in vitro and in vivo (CQCP, and amodiaquine plus pyrimethamine-sulphadoxine (AQPS on gametocyte production were evaluated in 157 children with acute, symptomatic, uncomplicated falciparum malaria who were treated with these drugs. PS was significantly less effective than CQCP or AQPS at clearing asexual parasitaemia or other symptoms of malaria. Gametocyte carriage on days 3, 7, and 14 were significantly higher in those treated with PS. The ratio of the density (per µl blood of peripheral young gametocyte (PYG, that is, < stage III to peripheral mature gametocyte (PMG, that is, stage IV and V, an index of continuing generation of gametocytes, rose to 1 by day 7 of treatment in those treated with PS, but remained consistently below 1 in the other treatment groups. PYG-PMG density ratio increased significantly from day 0-14 in those treated with PS and CQCP (chi2 = 76, P = 0.000001 and chi2 = 42.2, P = 0.00001, respectively but decreased significantly in those treated with AQPS (chi2 = 53.2, P = 0.000001. Both PS-sensitive and -resistant infections generated PYG (18 of 29 vs 13 of 20, chi2 = 0.04, P = 0.93 but PYG was present only in those with resistant response to CQCP. Combination of PS with amodiaquine (AQ, that is, (AQPS resulted in less production of PYG, but in this setting, PYG was not indicative of response to AQPS. These data indicate that PS enhanced production or release of young gametocytes when used alone, but generated less young gametocytes when used in combination with AQ. PYG may be used as an indicator of response to CQCP but not PS or PS-based combination drugs.

  9. A comparative hospital-based observational study of mono- and co-infections of malaria, dengue virus and scrub typhus causing acute undifferentiated fever.

    Science.gov (United States)

    Ahmad, S; Dhar, M; Mittal, G; Bhat, N K; Shirazi, N; Kalra, V; Sati, H C; Gupta, V

    2016-04-01

    Positive serology for dengue and/or scrub typhus infection with/without positive malarial smear (designated as mixed or co-infection) is being increasingly observed during epidemics of acute undifferentiated febrile illnesses (AUFIs). We planned to study the clinical and biochemical spectrum of co-infections with Plasmodium sp., dengue virus and scrub typhus and compare these with mono-infection by the same organisms. During the period from December 2012 to December 2013, all cases presenting with AUFIs to a single medical unit of a referral centre in Garhwal region of the north Indian state of Uttarakhand were retrospectively selected and categorised aetiologically as co-infections, malaria, dengue or scrub typhus. The groups thus created were compared in terms of demographic, clinical, biochemical and outcome parameters. The co-infection group (n = 49) was associated with milder clinical manifestations, fewer, milder and non-progressive organ dysfunction, and lesser need for intensive care, mechanical ventilation and dialysis as compared to mono-infections. When co-infections were sub-grouped and compared with the relevant mono-infections, there were differences in certain haematological and biochemical parameters; however, this difference did not translate into differential outcomes. Scrub typhus mono-infection was associated with severe disease in terms of both morbidity and mortality. Malaria, dengue and scrub typhus should be routinely tested in all patients with AUFIs. Co-infections, whether true or due to serological cross-reactivity, appear to be a separate entity so far as presentation and morbidity is concerned. Further insight is needed into the mechanism and identification of the protective infection.

  10. Patient age does not affect mefloquine concentrations in erythrocytes and plasma during the acute phase of falciparum malaria

    Directory of Open Access Journals (Sweden)

    José Luiz Fernandes Vieira

    Full Text Available Abstract Objective To evaluate whether patient age has a significant impact on mefloquine concentrations in the plasma and erythrocytes over the course of treatment for uncomplicated falciparum malaria. Methods A total of 20 children aged between 8 and 11 years and 20 adult males aged between 22 and 41 years with uncomplicated falciparum malaria were enrolled in the study. Mefloquine was administered to patients in both age groups at a dose of 20 mg kg−1. The steady-state drug concentrations were measured by reversed-phase high performance liquid chromatography. Results All patients had an undetectable mefloquine concentration on day 0. In adults, the plasma mefloquine concentrations ranged from 770 to 2930 ng mL−1 and the erythrocyte concentrations ranged from 2000 to 6030 ng mL−1. In children, plasma mefloquine concentrations ranged from 881 to 3300 ng mL−1 and erythrocyte concentrations ranged from 3000 to 4920 ng mL−1. There was no significant correlation between mefloquine concentrations in the plasma and erythrocytes in either adults or children. Conclusion In the present study, we observed no effect of patient age on the steady-state concentrations of mefloquine in the plasma and erythrocytes. We found that the mefloquine concentration in the erythrocytes was approximately 2.8-times higher than in the plasma. There were no significant correlations between mefloquine concentrations in the erythrocytes and plasma for either age group.

  11. [Malaria websites].

    Science.gov (United States)

    Genton, B

    2007-05-16

    One click on google.com, key-word "Malaria", 24,900,000 entries. How to choose among this jungle of websites? Ten sites are proposed to meet the needs of the general practitioner They are categorized by focus of interest, namely 1) detailed information on pre- and post-travel advice and management of travelers with illness upon return, 2) the essential on the parasite, the diagnosis and the treatment, 3) the malaria problem worldwide and 4) malaria maps.

  12. Laboratory indicators of the diagnosis and course of imported malaria

    DEFF Research Database (Denmark)

    Gjørup, Ida E; Vestergaard, Lasse S; Møller, Kirsten

    2007-01-01

    When travellers return from malaria-endemic areas and present to hospital with fever, microscopy of blood smears remains the leading method to verify a suspected diagnosis of malaria. Additional laboratory abnormalities may, however, also be indicative of acute malaria infection. We monitored......, in particular thrombocyte counts, in guiding the clinician managing a returning traveller with fever....

  13. Cerebral malaria Malaria cerebral

    Directory of Open Access Journals (Sweden)

    Silvia Blair Trujillo

    2003-03-01

    Full Text Available Is the most common complication of P. falciparum malaria; nearly 90% of people who have suffered CM can recover without neurological problems. Currently there are four hypotheses that explain pathogenesis of CM: cytoadherence and sequestering of parasitized red blood cells to cerebral capillaries; rosette formation and parasitized red blood cells agglutination; production of cytokines and activation of second messengers and opening of the blood-brain barrier. However the main question remains to be answered; how the host-parasite interaction in the vascular space interferes transiently with cerebral function? Recently, the beta amyloid precursor peptide has been employed as marker of neural injury in CM. It is expected that the beta amyloid precursor peptide will help to understand the pathogenesis of CM in complicated patients of endemic areas of Colombia. La malaria Cerebral (MC es la complicación más frecuente de la malaria por P. falciparum; aproximadamente el 90% de las personas que la han padecido se recuperan completamente sin secuelas neurológicas. Aún no se conoce con claridad su patogénesis pero se han postulado cuatro hipótesis o mecanismos posibles: 1 citoadherencia y secuestro de glóbulos rojos parasitados en la microvasculatura cerebral; 2 formación de rosetas y aglutinación de glóbulos rojos parasitados; 3 producción de citoquinas y activación de segundos mensajeros y, 4 apertura de la barrera hematoencefálica. Sin embargo, queda un interrogante sin resolver aún: ¿qué proceso se lleva a cabo para que el parásito, desde el espacio microvascular, pueda interferir transitoriamente con la función cerebral? Recientemente se ha utilizado el precursor de la proteína b-Amiloide como un marcador de daño neuronal en MC; este precursor será de gran ayuda en futuras investigaciones realizadas en nuestro medio que aporten información para comprender la patogénesis de la MC.

  14. Malaria Matters

    Centers for Disease Control (CDC) Podcasts

    2008-04-18

    This podcast gives an overview of malaria, including prevention and treatment, and what CDC is doing to help control and prevent malaria globally.  Created: 4/18/2008 by National Center for Zoonotic, Vector-Borne, and Enteric Diseases (NCZVED).   Date Released: 4/18/2008.

  15. Rodents And Other Gnawers.

    Science.gov (United States)

    Naturescope, 1986

    1986-01-01

    Presents information about rodents and lagomorphs, including definitions and the characteristics of these animals. Contains teaching activities such as "Habitats for Hoppers,""Cartoon Gnawers," and "The Great Rodent Expedition." Reproducible handouts for two of the activities are provided. (TW)

  16. Plasma glutamine levels and falciparum malaria.

    Science.gov (United States)

    Cowan, G; Planche, T; Agbenyega, T; Bedu-Addo, G; Owusu-Ofori, A; Adebe-Appiah, J; Agranoff, D; Woodrow, C; Castell, L; Elford, B; Krishna, S

    1999-01-01

    Glutamine deficiency is associated with increased rates of sepsis and mortality, which can be prevented by glutamine supplementation. Changes in glutamine concentration were examined in Ghanaian children with acute falciparum malaria and control cases. The mean (SD) plasma glutamine concentration was lower in patients with acute malaria (401 (82) mumol/L, n = 50) than in control patients (623 (67) mumol/L, n = 7; P sepsis and dyserythropoeisis.

  17. The CD14+CD16+ inflammatory monocyte subset displays increased mitochondrial activity and effector function during acute Plasmodium vivax malaria.

    Directory of Open Access Journals (Sweden)

    Lis R V Antonelli

    2014-09-01

    Full Text Available Infection with Plasmodium vivax results in strong activation of monocytes, which are important components of both the systemic inflammatory response and parasite control. The overall goal of this study was to define the role of monocytes during P. vivax malaria. Here, we demonstrate that P. vivax-infected patients display significant increase in circulating monocytes, which were defined as CD14(+CD16- (classical, CD14(+CD16(+ (inflammatory, and CD14loCD16(+ (patrolling cells. While the classical and inflammatory monocytes were found to be the primary source of pro-inflammatory cytokines, the CD16(+ cells, in particular the CD14(+CD16(+ monocytes, expressed the highest levels of activation markers, which included chemokine receptors and adhesion molecules. Morphologically, CD14(+ were distinguished from CD14lo monocytes by displaying larger and more active mitochondria. CD14(+CD16(+ monocytes were more efficient in phagocytizing P. vivax-infected reticulocytes, which induced them to produce high levels of intracellular TNF-α and reactive oxygen species. Importantly, antibodies specific for ICAM-1, PECAM-1 or LFA-1 efficiently blocked the phagocytosis of infected reticulocytes by monocytes. Hence, our results provide key information on the mechanism by which CD14(+CD16(+ cells control parasite burden, supporting the hypothesis that they play a role in resistance to P. vivax infection.

  18. Malaria and Travelers

    Science.gov (United States)

    ... a CDC Malaria Branch clinician. malaria@cdc.gov Malaria and Travelers Recommend on Facebook Tweet Share Compartir ... may be at risk for infection. Determine if malaria transmission occurs at the destinations Obtain a detailed ...

  19. Malaria Treatment (United States)

    Science.gov (United States)

    ... a CDC Malaria Branch clinician. malaria@cdc.gov Malaria Treatment (United States) Recommend on Facebook Tweet Share Compartir Treatment of Malaria: Guidelines For Clinicians (United States) Download PDF version ...

  20. Lassa fever or lassa hemorrhagic fever risk to humans from rodent-borne zoonoses.

    Science.gov (United States)

    El-Bahnasawy, Mamdouh M; Megahed, Laila Abdel-Mawla; Abdalla Saleh, Hala Ahmed; Morsy, Tosson A

    2015-04-01

    Viral hemorrhagic fevers (VHFs) typically manifest as rapidly progressing acute febrile syndromes with profound hemorrhagic manifestations and very high fatality rates. Lassa fever, an acute hemorrhagic fever characterized by fever, muscle aches, sore throat, nausea, vomiting, diarrhea and chest and abdominal pain. Rodents are important reservoirs of rodent-borne zoonosis worldwide. Transmission rodents to humans occur by aerosol spread, either from the genus Mastomys rodents' excreta (multimammate rat) or through the close contact with infected patients (nosocomial infection). Other rodents of the genera Rattus, Mus, Lemniscomys, and Praomys are incriminated rodents hosts. Now one may ask do the rodents' ectoparasites play a role in Lassa virus zoonotic transmission. This paper summarized the update knowledge on LHV; hopping it might be useful to the clinicians, nursing staff, laboratories' personals as well as those concerned zoonoses from rodents and rodent control.

  1. Rodent Research-1 Validation of Rodent Hardware

    Science.gov (United States)

    Globus, Ruth; Beegle, Janet

    2013-01-01

    To achieve novel science objectives, validation of a rodent habitat on ISS will enable - In-flight analyses during long duration spaceflight- Use of genetically altered animals- Application of modern analytical techniques (e.g. genomics, proteomics, and metabolomics)

  2. Defining species specific genome differences in malaria parasites.

    Science.gov (United States)

    Liew, Kingsley J L; Hu, Guangan; Bozdech, Zbynek; Peter, Preiser R

    2010-02-23

    In recent years a number of genome sequences for different plasmodium species have become available. This has allowed the identification of numerous conserved genes across the different species and has significantly enhanced our understanding of parasite biology. In contrast little is known about species specific differences between the different genomes partly due to the lower sequence coverage and therefore relatively poor annotation of some of the draft genomes particularly the rodent malarias parasite species. To improve the current annotation and gene identification status of the draft genomes of P. berghei, P. chabaudi and P. yoelii, we performed genome-wide comparisons between these three species. Through analyses via comparative genome hybridizations using a newly designed pan-rodent array as well as in depth bioinformatics analysis, we were able to improve on the coverage of the draft rodent parasite genomes by detecting orthologous genes between these related rodent parasite species. More than 1,000 orthologs for P. yoelii were now newly associated with a P. falciparum gene. In addition to extending the current core gene set for all plasmodium species this analysis also for the first time identifies a relatively small number of genes that are unique to the primate malaria parasites while a larger gene set is uniquely conserved amongst the rodent malaria parasites. These findings allow a more thorough investigation of the genes that are important for host specificity in malaria.

  3. Pyronaridine-Artesunate versus Chloroquine in Patients with Acute Plasmodium vivax Malaria: A Randomized, Double-Blind, Non-Inferiority Trial

    OpenAIRE

    Yi Poravuth; Duong Socheat; Ronnatrai Rueangweerayut; Chirapong Uthaisin; Aung Pyae Phyo; Neena Valecha; B. H. Krishnamoorthy Rao; Emiliana Tjitra; Asep Purnama; Isabelle Borghini-Fuhrer; Stephan Duparc; Chang-Sik Shin; Lawrence Fleckenstein

    2011-01-01

    BACKGROUND: New antimalarials are needed for P. vivax and P. falciparum malaria. This study compared the efficacy and safety of pyronaridine-artesunate with that of chloroquine for the treatment of uncomplicated P. vivax malaria. METHODS AND FINDINGS: This phase III randomized, double-blind, non-inferiority trial included five centers across Cambodia, Thailand, India, and Indonesia. In a double-dummy design, patients (aged >3-≤ 60 years) with microscopically confirmed P. vivax mono-infection ...

  4. Malaria-induced renal damage: facts and myths.

    Science.gov (United States)

    Ehrich, Jochen H H; Eke, Felicia U

    2007-05-01

    Malaria infections repeatedly have been reported to induce nephrotic syndrome and acute renal failure. Questions have been raised whether the association of a nephrotic syndrome with quartan malaria was only coincidental, and whether the acute renal failure was a specific or unspecific consequence of Plasmodium falciparum infection. This review attempts to answer questions about "chronic quartan malaria nephropathy" and "acute falciparum malaria nephropathy". The literature review was performed on all publications on kidney involvement in human and experimental malarial infections accessible in PubMed or available at the library of the London School of Hygiene and Tropical Medicine. The association of a nephrotic syndrome with quartan malaria was mostly described before 1975 in children and rarely in adult patients living in areas endemic for Plasmodium malariae. The pooled data on malaria-induced acute renal failure included children and adults acquiring falciparum malaria in endemic areas either as natives or as travellers from non-tropical countries. Non-immunes (not living in endemic areas) had a higher risk of developing acute renal failure than semi-immunes (living in endemic areas). Children with cerebral malaria had a higher rate and more severe course of acute renal failure than children with mild malaria. Today, there is no evidence of a dominant role of steroid-resistant and chronic "malarial glomerulopathies" in children with a nephrotic syndrome in Africa. Acute renal failure was a frequent and serious complication of falciparum malaria in non-immune adults. However, recently it has been reported more often in semi-immune African children with associated morbidity and mortality.

  5. Atypical lymphocytes in malaria mimicking dengue infection in Thailand

    Directory of Open Access Journals (Sweden)

    Polrat Wilairatana

    2010-09-01

    Full Text Available Polrat Wilairatana1, Noppadon Tangpukdee1, Sant Muangnoicharoen1, Srivicha Krudsood2, Shigeyuki Kano31Department of Clinical Tropical Medicine, 2Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; 3Department of Tropical Medicine and Malaria, Research Institute, National Center for Global Health and Medicine, Tokyo, JapanAbstract: Patients with uncomplicated falciparum or vivax malaria usually present with acute febrile illness and thrombocytopenia similar to dengue infection. We retrospectively studied atypical lymphocytes (AL and atypical lymphocytosis (ALO, defined as AL > 5% of total white blood cells in 1310 uncomplicated malaria patients. In 718 falciparum malaria patients, AL and ALO on day 0 were found in 53.2% and 5.7% of the patients, respectively, with median AL on admission of 1% (range 0%–10%, whereas in 592 vivax malaria patients, AL and ALO on day 0 were found in 55.4% and 9.5% of the patients, respectively, with median AL on admission of 1% (range 0%–14%. After antimalarial treatment, AL and ALO declined in both falciparum and vivax malaria. However, AL and ALO remained in falciparum malaria on days 7, 14, and 21, whereas AL and ALO remained in vivax malaria on days 7, 14, 21, and 28. In both falciparum and vivax malaria patients, there was a positive correlation between AL and total lymphocytes, but a negative correlation between AL and highest fever on admission, white blood cells, and neutrophils, eosinophils, and platelets (P < 0.05. In conclusion, AL or ALO may be found in uncomplicated falciparum and vivax malaria mimicking dengue infection. In tropical countries where both dengue and malaria are endemic, presence of AL or ALO in any acute febrile patients with thrombocytopenia (similar to the findings in dengue malaria could not be excluded. Particularly if the patients have risk of malaria infection, confirmative microscopic examination for malaria should be carried out

  6. falciparum malaria?

    African Journals Online (AJOL)

    Wassermann reactions and then lupus anticoagu- lant are now known ... ACA levels in the patient group, or between the ... bral malaria could lead to more effective therapy and an improved ... each patient and a physical examination performed. Particular .... a thrombotic subset of SLE: distinct profiles for epitope specificiry.

  7. Kompliceret malaria

    DEFF Research Database (Denmark)

    Rønn, A M; Bygbjerg, Ib Christian; Jacobsen, E

    1989-01-01

    An increasing number of cases of malaria, imported to Denmark, are caused by Plasmodium falciparum and severe and complicated cases are more often seen. In the Department of Infectious Diseases, Rigshospitalet, 23 out of 32 cases, hospitalized from 1.1-30.6.1988, i.e. 72%, were caused by P...

  8. Cytokine Profiles in Malawian Children Presenting with Uncomplicated Malaria, Severe Malarial Anemia, and Cerebral Malaria.

    Science.gov (United States)

    Mandala, Wilson L; Msefula, Chisomo L; Gondwe, Esther N; Drayson, Mark T; Molyneux, Malcolm E; MacLennan, Calman A

    2017-04-01

    Proinflammatory cytokines are involved in clearance of Plasmodium falciparum, and very high levels of these cytokines have been implicated in the pathogenesis of severe malaria. In order to determine how cytokines vary with disease severity and syndrome, we enrolled Malawian children presenting with cerebral malaria (CM), severe malarial anemia (SMA), and uncomplicated malaria (UCM) and healthy controls. We analyzed serum cytokine concentrations in acute infection and in convalescence. With the exception of interleukin 5 (IL-5), cytokine concentrations were highest in acute CM, followed by SMA, and were only mildly elevated in UCM. Cytokine concentrations had fallen to control levels when remeasured at 1 month of convalescence in all three clinical malaria groups. Ratios of IL-10 to tumor necrosis factor alpha (TNF-α) and of IL-10 to IL-6 followed a similar pattern. Children presenting with acute CM had significantly higher concentrations of TNF-α (P Mandala et al.

  9. Plasmodium interspersed repeats: the major multigene superfamily of malaria parasites

    Science.gov (United States)

    Janssen, Christoph S.; Phillips, R. Stephen; Turner, C. Michael R.; Barrett, Michael P.

    2004-01-01

    Functionally related homologues of known genes can be difficult to identify in divergent species. In this paper, we show how multi-character analysis can be used to elucidate the relationships among divergent members of gene superfamilies. We used probabilistic modelling in conjunction with protein structural predictions and gene-structure analyses on a whole-genome scale to find gene homologies that are missed by conventional similarity-search strategies and identified a variant gene superfamily in six species of malaria (Plasmodium interspersed repeats, pir). The superfamily includes rif in P.falciparum, vir in P.vivax, a novel family kir in P.knowlesi and the cir/bir/yir family in three rodent malarias. Our data indicate that this is the major multi-gene family in malaria parasites. Protein localization of products from pir members to the infected erythrocyte membrane in the rodent malaria parasite P.chabaudi, demonstrates phenotypic similarity to the products of pir in other malaria species. The results give critical insight into the evolutionary adaptation of malaria parasites to their host and provide important data for comparative immunology between malaria parasites obtained from laboratory models and their human counterparts. PMID:15507685

  10. The MAM rodent model of schizophrenia.

    Science.gov (United States)

    Lodge, Daniel J

    2013-01-01

    Rodent models of human disease are essential to obtain a better understanding of disease pathology, the mechanism of action underlying conventional treatments, as well as for the generation of novel therapeutic approaches. There are a number of rodent models of schizophrenia based on either genetic manipulations, acute or sub-chronic drug administration, or developmental disturbances. The prenatal methylazoxymethanol acetate (MAM) rodent model is a developmental disruption model gaining increased attention because it displays a number of histological, neurophysiological, and behavioral deficits analogous to those observed in schizophrenia patients. This unit describes the procedures required to safely induce the MAM phenotype in rats. In addition, we describe a simple behavioral procedure, amphetamine-induced hyperlocomotion, which can be utilized to verify the MAM phenotype.

  11. Comprehensive evaluation of peripheral nerve regeneration in the acute healing phase using tissue clearing and optical microscopy in a rodent model.

    Science.gov (United States)

    Jung, Yookyung; Ng, Joanna H; Keating, Cameron P; Senthil-Kumar, Prabhu; Zhao, Jie; Randolph, Mark A; Winograd, Jonathan M; Evans, Conor L

    2014-01-01

    Peripheral nerve injury (PNI), a common injury in both the civilian and military arenas, is usually associated with high healthcare costs and with patients enduring slow recovery times, diminished quality of life, and potential long-term disability. Patients with PNI typically undergo complex interventions but the factors that govern optimal response are not fully characterized. A fundamental understanding of the cellular and tissue-level events in the immediate postoperative period is essential for improving treatment and optimizing repair. Here, we demonstrate a comprehensive imaging approach to evaluate peripheral nerve axonal regeneration in a rodent PNI model using a tissue clearing method to improve depth penetration while preserving neural architecture. Sciatic nerve transaction and end-to-end repair were performed in both wild type and thy-1 GFP rats. The nerves were harvested at time points after repair before undergoing whole mount immunofluorescence staining and tissue clearing. By increasing the optic depth penetration, tissue clearing allowed the visualization and evaluation of Wallerian degeneration and nerve regrowth throughout entire sciatic nerves with subcellular resolution. The tissue clearing protocol did not affect immunofluorescence labeling and no observable decrease in the fluorescence signal was observed. Large-area, high-resolution tissue volumes could be quantified to provide structural and connectivity information not available from current gold-standard approaches for evaluating axonal regeneration following PNI. The results are suggestive of observed behavioral recovery in vivo after neurorrhaphy, providing a method of evaluating axonal regeneration following repair that can serve as an adjunct to current standard outcomes measurements. This study demonstrates that tissue clearing following whole mount immunofluorescence staining enables the complete visualization and quantitative evaluation of axons throughout nerves in a PNI model

  12. Malaria-filaria coinfection in mice makes malarial disease more severe unless filarial infection achieves patency.

    Science.gov (United States)

    Graham, Andrea L; Lamb, Tracey J; Read, Andrew F; Allen, Judith E

    2005-02-01

    Coinfections are common in natural populations, and the literature suggests that helminth coinfection readily affects how the immune system manages malaria. For example, type 1-dependent control of malaria parasitemia might be impaired by the type 2 milieu of preexisting helminth infection. Alternatively, immunomodulatory effects of helminths might affect the likelihood of malarial immunopathology. Using rodent models of lymphatic filariasis (Litomosoides sigmodontis) and noncerebral malaria (clone AS Plasmodium chabaudi chabaudi), we quantified disease severity, parasitemia, and polyclonal splenic immune responses in BALB/c mice. We found that coinfected mice, particularly those that did not have microfilaremia (Mf(-)), had more severe anemia and loss of body mass than did mice with malaria alone. Even when controlling for parasitemia, malaria was most severe in Mf(-) coinfected mice, and this was associated with increased interferon- gamma responsiveness. Thus, in Mf(-) mice, filariasis upset a delicate immunological balance in malaria infection and exacerbated malaria-induced immunopathology.

  13. In vivo imaging of neuroinflammation: a comparative study between [{sup 18}F]PBR111, [{sup 11}C]CLINME and [{sup 11}C]PK11195 in an acute rodent model

    Energy Technology Data Exchange (ETDEWEB)

    Van Camp, Nadja [CEA, I2BM, SHFJ, Laboratoire d' Imagerie Moleculaire Experimentale (LIME), Orsay (France); INSERM U803, Orsay (France); University of Antwerp, Bio-Imaging Lab, Antwerp (Belgium); Boisgard, Raphael; Theze, Benoit; Viel, Thomas; Tavitian, Bertrand [CEA, I2BM, SHFJ, Laboratoire d' Imagerie Moleculaire Experimentale (LIME), Orsay (France); INSERM U803, Orsay (France); Kuhnast, Bertrand; Dolle, Frederic [CEA, I2BM, SHFJ, Laboratoire d' Imagerie Moleculaire Experimentale (LIME), Orsay (France); Gregoire, Marie-Claude; Katsifis, Andrew [ANSTO, Radiopharmaceutical Research Institute, Lucas Heights (Australia); Chauveau, Fabien [CEA, I2BM, SHFJ, Laboratoire d' Imagerie Moleculaire Experimentale (LIME), Orsay (France); INSERM U803, Orsay (France); CREATIS-LRMN, CNRS, UMR 5220, Lyon (France); INSERM U630, Lyon (France); Boutin, Herve [University of Manchester, Faculty of Life Sciences, Manchester (United Kingdom)

    2010-05-15

    The key role of neuroinflammation in acute and chronic neurological disorders has stimulated the search for specific radiotracers targeting the peripheral benzodiazepine receptor (PBR)/18 kDa translocator protein (TSPO), a hallmark of neuroinflammation. Here we evaluate the new radiotracer for positron emission tomography (PET) [{sup 18}F]PBR111 in a rodent model of acute inflammation and compare it with [{sup 11}C]CLINME, an {sup 11}C-labelled tracer of the same chemical family, and with the isoquinolinic carboxamide [{sup 11}C]PK11195. We studied radiometabolites by HPLC, in vitro binding by autoradiography and in vivo brain kinetics as well as in vivo specificity of binding using PET imaging. We show that this radiotracer has a high in vitro specificity for PBR/TSPO versus central benzodiazepine receptors, as reflected by the drastic reduction of its binding to target tissue by addition of PK11195 or PBR111, while addition of flumazenil does not affect binding. Only intact [{sup 18}F]PBR111 is detected in brain up to 60 min after i.v. injection, and PET imaging shows an increased uptake in the lesion as compared to the contralateral side as early as 6 min after injection. Administration of an excess of PK11195 and PBR111, 20 min after [{sup 18}F]PBR111 administration, induces a rapid and complete displacement of [{sup 18}F]PBR111 binding from the lesion. Modelling of the PET data using the simplified reference tissue model showed increased binding potential (BP) in comparison to [{sup 11}C]PK11195. [{sup 18}F]PBR111 is a metabolically stable tracer with a high specific in vitro and in vivo binding to TSPO. In addition, considering the longer half-life of {sup 18}F over {sup 11}C, these results support [{sup 18}F]PBR111 as a promising PET tracer of the PBR/TSPO for neuroinflammation imaging. (orig.)

  14. Antidepressant and anti-anxiety like effects of 4i (N-(3-chloro-2-methylphenyl) quinoxalin-2-carboxamide), a novel 5-HT3 receptor antagonist in acute and chronic neurobehavioral rodent models.

    Science.gov (United States)

    Gupta, Deepali; Radhakrishnan, Mahesh; Thangaraj, Devadoss; Kurhe, Yeshwant

    2014-07-15

    Depression and anxiety are the most debilitating mood disorders with poor therapeutic recovery rates. In the last decades, 5-HT3 receptor antagonists have been identified as potential agents for mood disorders. The current investigation focuses on evaluating the, antidepressant and anti-anxiety like effects of a novel 5-HT3 antagonist, 4i (N-(3-chloro-2-methylphenyl) quinoxalin-2-carboxamide). Preliminary, in vitro 5-HT3 receptor binding affinity was performed in isolated longitudinal muscle-myenteric plexus from the guinea pig ileum. Consequently, neurobehavioral effects of 4i in acute and chronic rodent models were evaluated. In addition, involvement of serotonergic system in the postulated effects of the compound was analyzed by in vivo assay. in vitro, 4i demonstrated high 5-HT3 receptor antagonistic activity (pA2, 7.6). in vivo acute study, 4i exhibited decreased duration of immobility in forced swim and tail suspension tests, and increased exploratory parameters as number and duration of nose-poking in hole board test and latency and time spent in aversive brightly illuminated light chamber in light-dark model. Moreover, in chronic model of depression, i.e., olfactory bulbectomy with behavioral deficits, 4i reversed depressive anhedonia in sucrose preference test and anxious hyperactive behavior in open field test in rats. Furthermore, synergistic effect of 4i with fluoxetine (a selective serotonin reuptake inhibitor) and inhibitory effect of 1-(m-chlorophenyl)-biguanide (a 5-HT3 receptor agonist) revealed serotonergic modulation by 4i mediated 5-HT3 receptor antagonism, which was further confirmed by potentiation of 5-hydroxytryptophan (a serotonin synthesis precursor) induced head twitch response. These findings suggest the potential antidepressant and anti-anxiety like effects of 4i, which may be related to the modulation of serotonergic system. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. UK malaria treatment guidelines 2016.

    Science.gov (United States)

    Lalloo, David G; Shingadia, Delane; Bell, David J; Beeching, Nicholas J; Whitty, Christopher J M; Chiodini, Peter L

    2016-06-01

    . Most patients treated for P. falciparum malaria should be admitted to hospital for at least 24 h as patients can deteriorate suddenly, especially early in the course of treatment. In specialised units seeing large numbers of patients, outpatient treatment may be considered if specific protocols for patient selection and follow up are in place. 10. Uncomplicated P. falciparum malaria should be treated with an artemisinin combination therapy (Grade 1A). Artemether-lumefantrine (Riamet(®)) is the drug of choice (Grade 2C) and dihydroartemisinin-piperaquine (Eurartesim(®)) is an alternative. Quinine or atovaquone-proguanil (Malarone(®)) can be used if an ACT is not available. Quinine is highly effective but poorly-tolerated in prolonged treatment and should be used in combination with an additional drug, usually oral doxycycline. 11. Severe falciparum malaria, or infections complicated by a relatively high parasite count (more than 2% of red blood cells parasitized) should be treated with intravenous therapy until the patient is well enough to continue with oral treatment. Severe malaria is a rare complication of P. vivax or P. knowlesi infection and also requires parenteral therapy. 12. The treatment of choice for severe or complicated malaria in adults and children is intravenous artesunate (Grade 1A). Intravenous artesunate is unlicensed in the EU but is available in many centres. The alternative is intravenous quinine, which should be started immediately if artesunate is not available (Grade 1A). Patients treated with intravenous quinine require careful monitoring for hypoglycemia. 13. Patients with severe or complicated malaria should be managed in a high-dependency or intensive care environment. They may require haemodynamic support and management of: acute respiratory distress syndrome, disseminated intravascular coagulation, acute kidney injury, seizures, and severe intercurrent infections including Gram-negative bacteraemia/septicaemia. 14. Children with

  16. STUDY OF RENAL FAILURE IN MALARIA

    Directory of Open Access Journals (Sweden)

    Girish Pamappa

    2016-01-01

    Full Text Available Renal failure is a serious complication of malaria, with a mortality of 14 to 33%. In view of the significant morbidity and mortality due to acute renal failure in malaria, there is need to identify patients at an early stage and to intensify care given to reduce morbidity and mortality. AIMS  To evaluate the clinical profile of Acute Renal Failure (ARF in malaria.  To evaluate the factors associated with adverse outcome, relation of severity of renal impairment on final outcome in patients with ARF due to malaria. MATERIAL AND METHODS This study was conducted at a tertiary care hospital over a period of 12 months. STUDY DESIGN  Type of study: Prospective Analytical, Observational Study.  Sample Size: 50 patients admitted to ICU, Kidney Unit, and the Medicine Wards with Malaria and ARF. Inclusion Criteria Clinically screened patients with evidence of malarial parasites in the blood smears or by antigen detection with clinical features or biochemical evidence of acute renal failure. Exclusion Criteria  Presence of any disease or condition leading to ARF or affecting the outcome of malarial ARF.  Other causes of Fever, Jaundice and Oliguria, like Leptospirosis, Dengue. METHODOLOGY Fifty patients who fulfilled the inclusion criteria were interrogated with regards to the complaints, clinical signs. Blood tests were sent on admission. Details were recorded as per the clinical proforma. The patients were followed until their discharge/death. RESULTS Oliguria was present in only 30% of patients. 30% of patients received haemodialysis. The mortality was 12% for severe renal failure. On Univariate analysis, Acidosis and Cerebral malaria were highly significant predictors of mortality. Other significant predictors were Renal failure, Oliguria, Shock, DIC, Hyperparasitemia, Leukocytosis (TLC. On Multivariate analysis, Oliguria, Cerebral malaria, Acidosis, Shock and two or more complications were the independent predictors of mortality

  17. Zoonoses of rabbits and rodents.

    Science.gov (United States)

    Hill, William Allen; Brown, Julie Paige

    2011-09-01

    Millions of households in the US own rabbits or rodents, including hamsters, guinea pigs, and gerbils. Activities such as hunting and camping also involve human interactions with wild rabbits and rodents. In many environments, feral rabbits and rodents live in close proximity to humans, domesticated animals, and other wildlife. Education of rodent and rabbit owners and individuals with occupational or recreational exposures to these species is paramount to reduce the prevalence of zoonoses associated with rabbit and rodent exposure.

  18. 一株啶虫脒降解菌AC04的鼠类急性毒性评价%Acute toxicity evaluation of a strain of bacteria AC04 in rodent models

    Institute of Scientific and Technical Information of China (English)

    王旭; 张同刚; 郭进; 龚媛; 廖若宇; 徐梦霞; 刘雨杨; 曲云卿; 刘敦华

    2014-01-01

    目的:对从长期种植枸杞的土壤中分离筛选出的一株可高效降解农药啶虫脒的细菌 AC04进行急性毒性的安全性评价。方法将提取的AC04菌液对小鼠进行经口灌胃急性毒性实验;将表面喷洒菌悬液的枸杞对大鼠进行30 d喂养实验。结果经口急性毒性实验中实验小鼠行为、进食均正常,未出现中毒及死亡情况。观察期结束后,解剖动物主要脏器、器官,均未见明显异常改变。大鼠30d喂养实验中,实验动物的体征外观、行为、体重、血象等各项指标均正常,无明显中毒症状或不良反应。结论该菌株及其代谢产物对试验鼠未见明显毒性。%Objective To evaluate a new screened strain of bacteria AC04 found in the soil of long-term planting of Chinese wolfberry which can efficiently degrade the pesticide acetamiprid using rodent acute toxic-ity models. MethodsThe extracted fluid of bacteria was given to mice for acute toxicity experiment by ig. The rats were fed with wolfberry sprayed by the bacterial suspension for 30 d. Results The acute oral tox-icity tests showed the tested mice behaving and eating normal, without poisoning and death. At the end of the observation, the mice were dissected and the major organs showed no abnormalities. In the experiments of rats fed for 30 d, the appearance of experimental rats, as well as the behavior, body weight, and blood indicators showed normal, without obvious symptoms or adverse reactions. Conclusion The research showed that this strain of bacteria was harmless to the experimental animals.

  19. Adaptogenic and in vitro antioxidant activity of flavanoids and other fractions of Argyreia speciosa (Burm.f) Boj. in acute and chronic stress paradigms in rodents.

    Science.gov (United States)

    Habbu, P V; Mahadevan, K M; Kulkarni, P V; Daulatsingh, C; Veerapur, V P; Shastry, R A

    2010-01-01

    Argyreia speciosa (sweet) (Burm.f.) Boj. is an Ayurvedic rasayana plant used as an adaptogen. The present study reports the investigations done on the adaptogenic property of ethanol (EtAS; 100 and 200 mg/kg; po), ethyl acetate (EAAS; 100 and 200 mg/kg; po) fraction and flavanoids such as quercetin and kaempferol (25 mg/kg; po) of the root. Immobilization induced acute stress (AS; 3 days) and chronic stress (CS; 7 days) and swimming induced stress models were used to screen the anti-stress effect of the plant fractions and isolated flavanoids. The tested doses of EtAS and isolated flavanoids were able to produce significant effects in normalizing altered serum biochemical parameters and the severity of ulcer in both AS and CS models. Higher dose of EtAS, quercetin and kaempferol (25 mg/kg; po) were found to be significant in restoring the hypertrophy of adrenal gland and atrophy of spleen and thymus gland only in CS model. Greater swimming time was noted in the mice pretreated with tested doses of flavanoids and EtAS. In addition, levels of adrenal ascorbic acid and cortisol were restored compared to stress control group. EtAS exhibited significant scavenging effect of DPPH, hydroxyl radical and LPO. Thus, EtAS, quercetin and kaempferol are capable of increasing the capacity to tolerate non-specific stress in experimental animals, as evident from restoration of large number of parameters in the stress models studied. Bioactivity of EtAS may be due to the synergetic action of isolated flavanoids. Improvement in stress markers may be due its prolong effect of resistance to stress and partly due to free radical scavenging activity.

  20. Oroxylin-A rescues LPS-induced acute lung injury via regulation of NF-κB signaling pathway in rodents.

    Directory of Open Access Journals (Sweden)

    Tzu-Ling Tseng

    Full Text Available BACKGROUND AND PURPOSE: Successful drug treatment for sepsis-related acute lung injury (ALI remains a major clinical problem. This study was designed to assess the beneficial effects of post-treatment of oroxylin A (OroA, a flavonoid, in ameliorating lipopolysaccharides (LPS-induced lung inflammation and fatality. EXPERIMENTAL APPROACH: Rats were injected with LPS (10 mg/kg, iv to induce ALI, and OroA was given (15 mg/kg, iv 1 hr or 6 hrs after LPS challenge. Twenty four hrs after LPS challenge, biochemical changes in the blood and lung tissues, and morphological/histological alterations in the lung associated with inflammation and injury were examined. Therapeutic effect of OroA was assessed by measuring the survival rate in endotoxemic mice. KEY RESULTS: LPS (10 mg/kg, iv significantly altered WBC counts, elevated plasma tumor necrosis factor (TNF-α and nitric oxide (NO, increased pulmonary edema, thickened alveolar septa, and decreased survival rate. These changes were ameliorated by OroA (15 mg/kg, iv administered 1 hr or 6 hrs after LPS challenge. This post-treatment also significantly attenuated LPS-induced activation of nuclear factor-κB (NF-κB and the release of high mobility group box 1 (HMGB1 in lung tissues. Furthermore, post-treatment with OroA (60 mg/kg, ip administered 1 hr or 6 hrs after LPS challenge in mice significantly increased survival rate. CONCLUSION AND IMPLICATION: OroA administered after induction of ALI by LPS significantly prevent and revere lung tissues injuries with increased survival rate. Positive post-treatment effects of OroA suggest that OroA is a potentially useful candidate for managing lung inflammation in LPS-induced endotoxemia and septic shock.

  1. The largest fossil rodent

    Science.gov (United States)

    Rinderknecht, Andrés; Blanco, R. Ernesto

    2008-01-01

    The discovery of an exceptionally well-preserved skull permits the description of the new South American fossil species of the rodent, Josephoartigasia monesi sp. nov. (family: Dinomyidae; Rodentia: Hystricognathi: Caviomorpha). This species with estimated body mass of nearly 1000 kg is the largest yet recorded. The skull sheds new light on the anatomy of the extinct giant rodents of the Dinomyidae, which are known mostly from isolated teeth and incomplete mandible remains. The fossil derives from San José Formation, Uruguay, usually assigned to the Pliocene–Pleistocene (4–2 Myr ago), and the proposed palaeoenvironment where this rodent lived was characterized as an estuarine or deltaic system with forest communities. PMID:18198140

  2. Assessment of the Effects of Acute and Repeated Exposure to Blast Overpressure in Rodents: Towards a Greater Understanding of Blast and the Potential Ramifications for Injury in Humans Exposed to Blast

    Directory of Open Access Journals (Sweden)

    Stephen Thomas Ahlers

    2012-03-01

    Full Text Available Mild traumatic brain injury (mTBI resulting from exposure to improvised explosive devices (IEDs has fueled a requirement to develop animals models that mirror this condition using exposure to blast overpressure (BOP. En route to developing a model of repeated exposure to BOP we sought to initially characterize the effects of acute BOP exposure in rodents, focusing specifically on the levels of BOP exposure that produced clinical mTBI symptoms. We first measured BOP effects on gross motor function on a balance beam. Separate groups of unanesthetized rats were exposed (in different orientations to 40 kPa, 75 kPa and 120 kPa BOP exposure inside a pneumatically driven shock tube. Results demonstrated that rats exposed to 120 kPa demonstrated transient alterations or loss of consciousness indicated by a transient loss of righting and by increased latencies on the balance beam. The 120 kPa exposure was the threshold for overt pathology for acute BOP exposure with approximately 30% of rats presenting with evidence of subdural hemorrhage and cortical contusions. All animals exposed to 120 kPa BOP manifested evidence of significant pulmonary hemorrhage. Anterograde memory deficits were observed in rats exposed to 75 kPa facing the BOP wave and rats exposed to 120 kPa in the lateral (side orientation. We next assessed repeated exposure to either lateral or frontal 40 kPa BOP in anesthetized rats, once per day for 12 days. Results showed that repeated exposure in the frontal, but not side, orientation to the BOP wave produced a transitory learning deficit on a Morris water maze (MWM task as shown by significantly longer latencies to reach the submerged platform in the second and third blocks of a four block session. Implications of these data are discussed in relation to the manifestation of mTBI in military personnel exposed to IEDs. Finally, we suggest that there are multiple types of brain injury from blast.

  3. Fatal complications of Plasmodium vivax malaria: A series of three case reports

    Directory of Open Access Journals (Sweden)

    Deepak Sundriyal

    2013-01-01

    Full Text Available Plasmodium vivax malaria once thought to be benign, is now being seen increasingly as complicated disease in various manifestations. These complications include cerebral malaria, acute respiratory distress syndrome, acute pancreatitis, hepatic dysfunction, coagulopathy-associated hemorrhages, and others. Even if at the onset, disease appears benign, clinicians should be careful to watch for the complications and timely management.

  4. Uus Multiphonic Rodent

    Index Scriptorium Estoniae

    2009-01-01

    Tartus tegutsenud eksperimentaal-rock-duo Opium Flirt Eestisse jäänud liige Erki Hõbe (paarimees Ervin Trofimov tegutseb Ungaris) annab välja oma teise sooloalbumi nime all Multiphonic Rodent, heliplaadi "Astral Dance" esitluskontsert toimub 5. veebruaril Tallinnas baaris Juuksur

  5. Rodents of the Caribbean

    DEFF Research Database (Denmark)

    Fabre, Pierre-Henri; Mouatt, Julia Thidamarth Vilstrup; Raghavan, Maanasa;

    2014-01-01

    The Capromyidae (hutias) are endemic rodents of the Caribbean and represent a model of dispersal for non-flying mammals in the Greater Antilles. This family has experienced severe extinctions during the Holocene and its phylogenetic affinities with respect to other caviomorph relatives are still...

  6. Brief history of the clinical diagnosis of malaria: from Hippocrates to Osler

    Directory of Open Access Journals (Sweden)

    Cheston B. Cunha

    2008-08-01

    Full Text Available Since antiquity, malaria had a major impact on world history but this brief historical overview focuses on clinical features of malaria from Hippocrates to Osler. In antiquity, physicians tried to differentiate malaria from other acute fevers. The classic descriptions of malaria by Hippocrates in ancient Greece and Celsus in ancient Rome are excerpted here from the original Greek and Latin. Their clear clinical descriptions prove malaria was recognized in antiquity. In the modern era, it remains difficult to clinically differentiate malaria from typhoid fever. Since physicians used the term ‘typho-malaria’ to describe acute undifferentiated fevers a testimony to their lack of clinical acumen. Osler, the great clinician, by careful observation in clinical features and fever patterns was able to clearly differentiate malaria from typhoid fever as did the ancients.

  7. Incidence, severity, prognostic significance of thrombocytopenia in malaria

    Directory of Open Access Journals (Sweden)

    Bezwada Srinivasa Rao

    2015-01-01

    Full Text Available Background: Malaria is an infectious disease caused by plasmodium parasite. P. falciparum account for majority of morbidity and mortality. Thrombocytopenia and anaemia are the most frequently associated hematological complications in malaria. The low platelet count together with acute febrile syndrome emerged as the strongest predictor of malaria a finding that is frequent and present even before anemia and splenomegaly sets in. Severe thrombocytopenia is a good predictor of poor prognosis than mild and moderate thrombocytopenia. The aim is to study the incidence, severity, prognostic significance of thrombocytopenia in malaria. Methods: This was an observational and prospective study. The study enrolled 100 patients with thrombocytopenia and fever who were proven to have malaria either by peripheral smear or Quantitative Buffy Coat (QBC test or malarial antigen assay were included in the study and patients with thrombocytopenia due to other causes were excluded from the study. Platelet count was estimated on a fully automated quantitative analyzer. All the 100 patients were followed during the hospital stay and upto discharge or till the outcome. Results: The incidence of thrombocytopenia was 73% indicating a common association in malaria. Complicated malaria was observed in 58.80% of P. falciparum infection whereas 66% of P. vivax infection was associated with uncomplicated malaria. Severe thrombocytopenia showed positive correlation with severity of malaria. Thrombocytopenic patients with effective anti-malarial treatment showed 95.90% recovery and 3 patients 4.10% had mortality. Patients with severe thrombocytopenia were 8.5 times more likely to have complicated malaria with P <0.001 according to student and lsquo;t' test. Conclusion: Thrombocytopenia is the most common hematological finding in malaria. Severe thrombocytopenia showed positive correlation with complicated malaria and a good predictor of poor prognosis. Patients with classical

  8. [WHO's malaria program Roll Back Malaria].

    Science.gov (United States)

    Myrvang, B; Godal, T

    2000-05-30

    Malaria is one of the main health problems in the world with 300-500 millions cases yearly and about one million deaths, mainly children in Sub-Saharan Africa. In the 1990s the malaria problem in Africa has increased, although we have methods to control the disease. In 1998 the new secretary general of WHO, Gro Harlem Brundtland, established the Roll Back Malaria programme, with the aim to markedly reduce malaria morbidity and mortality. Governments in malaria-affected countries have to take the lead in Roll Back Malaria. Their health systems must be improved and malaria control integrated into the general health system, and the methods available for prevention and treatment have to be intensified and improved. At the same time, Roll Back Malaria will encourage and promote malaria research which hopefully will result in new medicines, vaccines and other tools which will improve the chances of reducing malaria-related deaths and suffering. Roll Back Malaria is a cabinet project within the WHO, and the organisation has a key role as manager, co-ordinator and monitor of the project. However, it depends for resources on international support and commitment from other UN bodies, the World Bank, governments in the western world, pharmaceutical industry, philanthropists and other sources. At present an optimistic view prevails, and the preliminary aim, to halve the malaria mortality by the year 2010, seems realistic even with the control methods of today. However, if research efforts result in new and better tools to combat the disease, the task will definitely be easier.

  9. Rapid reemergence of T cells into peripheral circulation following treatment of severe and uncomplicated Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Hviid, L; Kurtzhals, J A; Goka, B Q

    1997-01-01

    Frequencies and absolute numbers of peripheral T-cell subsets were monitored closely following acute Plasmodium falciparum malaria in 22 Ghanaian children from an area of hyperendemicity for seasonal malaria transmission. The children presented with cerebral or uncomplicated malaria (CM or UM...

  10. Stage-selective inhibition of rodent malaria by cyclosporine.

    Science.gov (United States)

    Murphy, J R; Baqar, S; Baker, R H; Roberts, E; Nickell, S P; Cole, G A

    1988-01-01

    The relative susceptibility of different developmental stages of Plasmodium berghei to cyclosporine was investigated in vivo. Within 12 h of receiving a single 25-mg/kg (body weight) dose of cyclosporine, mice with patent P. berghei infections uniformly exhibited a rapid fall in asexual parasite stages. Initially, ring forms and mature schizonts disappeared. Subsequently, trophozoites disappeared between 21 and 24 h, whereas gametocytes persisted for 36 h. In contrast, when cyclosporine was administered to mice 1 day before inoculation (100 mg/kg) with P. berghei sporozoites and for 2 consecutive days after inoculation (25 mg/kg), infections developed normally. When mice with patent infections were placed on prolonged cyclosporine therapy (25 mg/kg per day), parasitemia initially disappeared but often recrudesced. Recrudescent parasites were frequently resistant to cyclosporine (Csr). The Csr phenotype remained stable after serial passage of parasites in mice and after transmission through Anopheles stephensi mosquitoes, in which the capacity to produce oocysts was reduced. When infections of untreated mice were initiated with equal numbers of Csr and cyclosporine-susceptible (Css) parasites and then carried through two serial cycles of mosquito-to-mouse transmission without cyclosporine treatment, the Csr phenotype was lost. The results indicate that cyclosporine selectively inhibits asexual blood stages of P. berghei and favors the emergence of Csr parasites with diminished infectivity for mosquitoes. PMID:3288113

  11. [Physiopathology of cerebral malaria].

    Science.gov (United States)

    Ringwald, P

    1995-01-01

    Physiopathology of severe malaria is extremely complex and misappreciated. Sequestration of parasited red cells and role of cytokines are now accepted but we still have to discover why only a few people develop a severe malaria. A better knowledge of that physiopathology would allow the conception of new therapeutic strategies to reduce malaria mortality.

  12. Type II fatty acid synthesis is essential only for malaria parasite late liver stage development

    OpenAIRE

    Vaughan, Ashley M.; O'Neill, Matthew T.; Tarun, Alice S.; Camargo, Nelly; Phuong, Thuan M; Aly, Ahmed S I; Cowman, Alan F.; Kappe, Stefan H. I.

    2008-01-01

    Intracellular malaria parasites require lipids for growth and replication. They possess a prokaryotic type II fatty acid synthesis (FAS II) pathway that localizes to the apicoplast plastid organelle and is assumed to be necessary for pathogenic blood stage replication. However, the importance of FAS II throughout the complex parasite life cycle remains unknown. We show in a rodent malaria model that FAS II enzymes localize to the sporozoite and liver stage apicoplast. Targeted deletion of Fab...

  13. Studies of the Interaction of Human Malaria Parasites with the Metabolism of the Host Red Cell.

    Science.gov (United States)

    1977-06-15

    theme was the development of a treatment of malaria involving hyperooia which was effective in suppressing P vinckei in rats, but not P. berghei•.,-X...conditions in rodent malaries (Section D). A related study to this general theme was the development of a treatment of malaria involving hyperoxia which... thalassemia trait have significantly lower levels of ATP per red cell than individuals who do not have thalassemia trait. We confirmed this in Sardinia and

  14. Malaria. Can WHO roll back malaria?

    Science.gov (United States)

    Balter, M

    2000-10-20

    In October 1998, World Health Organization Director-General Gro Harlem Brundtland announced Roll Back Malaria, a multiagency crusade that aims to cut malaria mortality in half over the next 10 years. Brundtland might just be the one to pull it off, say numerous public health experts, although some researchers question whether the goal is realistic.

  15. Case Report: Severe and Complicated Cynomolgi Malaria in a Rhesus Macaque Resulted in Similar Histopathological Changes as Those Seen in Human Malaria.

    Science.gov (United States)

    J Joyner, Chester; Consortium, The MaHPIC; Wood, Jennifer S; Moreno, Alberto; Garcia, Anapatricia; Galinski, Mary R

    2017-08-01

    Histopathological data collected from patients with severe malaria have been instrumental for studying malaria pathogenesis. Animal models of malaria are critical to complement such studies. Here, the histopathological changes observed in a rhesus macaque with severe and complicated Plasmodium cynomolgi malaria are reported. The animal presented with thrombocytopenia, severe anemia, and hyperparasitemia during the acute infection. The macaque was given subcurative antimalarial treatment, fluid support, and a blood transfusion to treat the clinical complications, but at the time of transfusion, kidney function was compromised. These interventions did not restore kidney function, and the animal was euthanized due to irreversible renal failure. Gross pathological and histological examinations revealed that the lungs, kidneys, liver, spleen, and bone marrow exhibited abnormalities similar to those described in patients with malaria. Overall, this case report illustrates the similarities in the pathophysiological complications that can occur in human malaria and cynomolgi malaria in rhesus macaques.

  16. Malaria in Children.

    Science.gov (United States)

    Cohee, Lauren M; Laufer, Miriam K

    2017-08-01

    Malaria is a leading cause of morbidity and mortality in endemic areas, leading to an estimated 438,000 deaths in 2015. Malaria is also an important health threat to travelers to endemic countries and should be considered in evaluation of any traveler returning from a malaria-endemic area who develops fever. Considering the diagnosis of malaria in patients with potential exposure is critical. Prompt provision of effective treatment limits the complications of malaria and can be life-saving. Understanding Plasmodium species variation, epidemiology, and drug-resistance patterns in the geographic area where infection was acquired is important for determining treatment choices. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Therapeutic efficacy of artesunate-amodiaquine combinations and the plasma and saliva concentrations of desethylamodiaquine in children with acute uncomplicated Plasmodium falciparum malaria.

    Science.gov (United States)

    Sowunmi, Akintunde; Gbotosho, Grace O; Happi, Christian T; Okuboyejo, Titilope M; Sijuade, Abayomi O; Michael, Obaro S; Adewoye, Elsie O; Folarin, Onikepe

    2013-01-01

    The treatment efficacy of artesunate-amodiaquine (AQ) coformulated or copackaged, and the plasma and saliva concentrations of desethylamodiaquine (DEAQ), the active metabolite of AQ, were evaluated in 120 and 7 children, respectively, with uncomplicated Plasmodium falciparum malaria treated with oral daily doses of the 2 formulations for 3 days. All children recovered clinically. Fever clearance (1.1 ± 0.2 vs 1.0 ± 0 days) and parasite clearance times (21.1 ± 10.2 vs 19.0 ± 7.0 hours) in artesunate-AQ coformulated and artesunate-AQ copackaged treated children, respectively, were similar. All children remained aparasitemic for at least 28 days. Blood and saliva samples were collected over 35 days and DEAQ in plasma and saliva was determined by high-performance liquid chromatography. DEAQ was detectable in plasma and saliva within 40 minutes of oral administration of artesunate-AQ. DEAQ concentrations 7 days after the start of therapy were 247.8 and 125.1 ng/mL in plasma and saliva, respectively. The concentration-time curves of plasma and saliva in declining phases were approximately parallel giving a similar half-life of 169.1 ± 16.4 and 142.8 ± 6.5 hours in plasma and saliva, respectively. Clearance from plasma and saliva was also similar (335.6 and 443.4 mL·h·kg, respectively). Area under concentration-time curves (AUC0-35d) for plasma and saliva were 94,744.9 and 74,004.2 ng·mL·h, respectively. In general, Saliva-plasma concentration ratio was 0.25-0.4. DEAQ concentrations in saliva may be useful for monitoring therapy and for the evaluation of the disposition of AQ in children with falciparum malaria treated with AQ-based combination.

  18. Malaria og graviditet

    DEFF Research Database (Denmark)

    Hoffmann, A L; Rønn, A M; Langhoff-Roos, J

    1992-01-01

    In regions where malaria is endemism, the disease is a recognised cause of complications of pregnancy such as spontaneous abortion, premature delivery, intrauterine growth retardation and foetal death. Malaria is seldom seen in pregnant women in Denmark but, during the past two years, the authors...... the patients but also their practitioners were unaware that malaria can occur several years after exposure. Three out of the four patients had employed malaria prophylaxis. As resistance to malarial prophylactics in current use is increasing steadily, chemoprophylaxis should be supplemented by mechanical...... protection against malaria and insect repellents. As a rule, malaria is treated with chloroquine. In cases of Falciparum malaria in whom chloroquine resistance is suspected, treatment with mefloquine may be employed although this should only be employed in cases of dire necessity in pregnant patients during...

  19. Gene disruption of Plasmodium falciparum p52 results in attenuation of malaria liver stage development in cultured primary human hepatocytes.

    Directory of Open Access Journals (Sweden)

    Ben C L van Schaijk

    Full Text Available Difficulties with inducing sterile and long lasting protective immunity against malaria with subunit vaccines has renewed interest in vaccinations with attenuated Plasmodium parasites. Immunizations with sporozoites that are attenuated by radiation (RAS can induce strong protective immunity both in humans and rodent models of malaria. Recently, in rodent parasites it has been shown that through the deletion of a single gene, sporozoites can also become attenuated in liver stage development and, importantly, immunization with these sporozoites results in immune responses identical to RAS. The promise of vaccination using these genetically attenuated sporozoites (GAS depends on translating the results in rodent malaria models to human malaria. In this study, we perform the first essential step in this transition by disrupting, p52, in P. falciparum an ortholog of the rodent parasite gene, p36p, which we had previously shown can confer long lasting protective immunity in mice. These P. falciparum P52 deficient sporozoites demonstrate gliding motility, cell traversal and an invasion rate into primary human hepatocytes in vitro that is comparable to wild type sporozoites. However, inside the host hepatocyte development is arrested very soon after invasion. This study reveals, for the first time, that disrupting the equivalent gene in both P. falciparum and rodent malaria Plasmodium species generates parasites that become similarly arrested during liver stage development and these results pave the way for further development of GAS for human use.

  20. Anti-phospholipid antibodies in patients with Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Jakobsen, P H; Morris-Jones, S D; Hviid, L;

    1993-01-01

    Plasma levels of antibodies against phosphatidylinositol (PI), phosphatidylcholine (PC) and cardiolipin (CL) were measured by enzyme-linked immunosorbent assay (ELISA) in patients from malaria endemic area of Sudan and The Gambia. Some Sudanese adults produced IgM antibodies against all three types...... of phospholipids (PL) during an acute Plasmodium falciparum infection. The anti-PL antibody titre returned to preinfection levels in most of the donors 30 days after the disease episode. IgG titres against PI, PC and CL were low. In Gambian children with malaria, IgM antibody titres against PI and PC were...... significantly higher in those with severe malaria than in those with mild malaria. These results show that a proportion of malaria patients produce anti-PL antibodies during infection and that titres of these antibodies are associated with the severity of disease....

  1. Rodent models of sleep apnea.

    Science.gov (United States)

    Davis, Eric M; O'Donnell, Christopher P

    2013-09-15

    Rodent models of sleep apnea have long been used to provide novel insight into the generation and predisposition to apneas as well as to characterize the impact of sleep apnea on cardiovascular, metabolic, and psychological health in humans. Given the significant body of work utilizing rodent models in the field of sleep apnea, the aims of this review are three-fold: first, to review the use of rodents as natural models of sleep apnea; second, to provide an overview of the experimental interventions employed in rodents to simulate sleep apnea; third, to discuss the refinement of rodent models to further our understanding of breathing abnormalities that occur during sleep. Given mounting evidence that sleep apnea impairs cognitive function, reduces quality of life, and exacerbates the course of multiple chronic diseases, rodent models will remain a high priority as a tool to interrogate both the pathophysiology and sequelae of breathing related abnormalities during sleep and to improve approaches to diagnosis and therapy.

  2. Geomagnetic field detection in rodents

    Energy Technology Data Exchange (ETDEWEB)

    Olcese, J.; Reuss, S.; Semm, P.

    1988-01-01

    In addition to behavioral evidence for the detection of earth-strength magnetic fields (MF) by rodents, recent investigations have revealed that electrophysiological and biochemical responses to MF occur in the pineal organ and retina of rodents. In addition, ferrimagnetic deposits have been identified in the ethmoidal regions of the rodent skull. These findings point to a new sensory phenomenon, which interfaces with many fields of biology, including neuroscience, psychophysics, behavioral ecology, chronobiology and sensory physiology.

  3. 双氢青蒿素与甲氟喹联用治疗恶性疟疾的疗效观察%Efficacy of dihydroartemisinin-mefloquine on acute uncomplicated falciparum malaria

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To evaluate the clinical efficacy of dihydroartemisinin—mefloquine on acute uncomplicated falciparum malaria. Methods Fifty-four patients with symptomatic falciparum malaria were allocated to receive oral dihydroartemisinin at a single dose of 120?mg on day 1, followed by mefloquine, 750?mg and 500?mg on days 2 and 3, respectively. Follow-up was performed on days 1,2,3,4,7,14,21, and 28. Results All patients had a rapid initial response to treatment. The parasite clearance time (PCT) after treatment was 30.7±3.6 hours. The fever subsidence time (FST) after treatment was 21.2±2.8 hours. Two patients had a recrudescence 21 and 25 days respectively after the disappearance of parasitemia, hence the recrudescence rate was 3.7% and the cure rate was 96.3%. No serious adverse effects were observed, only mild and transient nausea, vomiting and loss of appetite. Conclusion A combination of dihydroartemisinin and mefloquine is effective in the treatment of acute uncomplicated falciparum malaria.%目的观察双氢青蒿素与甲氟喹联用治疗急性无并发症恶性疟疾的临床疗效。 方法以首日单剂双氢青蒿素120mg顿服,次日及第三日甲氟喹750mg及500mg顿服的3日疗法,治疗无并发症的恶性疟54例,并于治疗后1、2、3、4、7、14、21和28天进行了随访。 结果 54例患者经治疗后全部临床治愈,平均疟原虫转阴时间为30.7±3.6小时。平均退热时间为21.2±2.8小时,54例中2例在疟原虫血症消失后第21、25天复燃,复燃率3.7%;治愈率96.3%。除少数病人发生轻微及短暂的恶心呕吐、纳差外,余未发现严重不良反应。 结论双氢青蒿素与甲氟喹联用 3日疗法治疗无并发症恶性疟疾具有良好疗效。

  4. Placental Malaria in Colombia: Histopathologic Findings in Plasmodium vivax and P. falciparum Infections

    Science.gov (United States)

    Carmona-Fonseca, Jaime; Arango, Eliana; Maestre, Amanda

    2013-01-01

    Studies on gestational malaria and placental malaria have been scarce in malaria-endemic areas of the Western Hemisphere. To describe the histopathology of placental malaria in Colombia, a longitudinal descriptive study was conducted. In this study, 179 placentas were studied by histologic analysis (112 with gestational malaria and 67 negative for malaria). Placental malaria was confirmed in 22.35%, 50.0% had previous infections, and 47.5% had acute infections. Typical malaria-associated changes were observed in 37%. The most common changes were villitis, intervillitis, deciduitis, increased fibrin deposition, increased syncytial knots, mononuclear (monocytes/macrophages and lymphocytes), polymorphonuclear cell infiltration, and trophozoites in fetal erythrocytes. No association was found between type of placental changes observed and histopathologic classification of placental malaria. The findings are consistent with those reported for placental malaria in other regions. Plasmodium vivax was the main parasite responsible for placental and gestational malaria, but its role in the pathogenesis of placental malaria was not conclusive. PMID:23546807

  5. Cytokines and dysregulation of the immune response in human malaria

    Directory of Open Access Journals (Sweden)

    M. Fátima C. Alves

    1992-01-01

    Full Text Available The dysregulation of the immune response by malaria parasite has been considered as a possible constraint to the effectiveness of malaria vaccination. In spite of the important role interleukin-I (IL-1 in malaria are lacking. We found that only 2 out of 35 subjectswith acute malaria showed increased levels of serum IL-1 alpha by enzyme immunoassay. To assess whether IL-1 could interfere with T- lymphocyte responses, blood mononuclear cells from patients infected with Plasmodium falciparum, P. vivax, or healthy subjects were cultured with phytohemagglutinin, and lymphocyte proliferation measured 72h later by 3H-thymidine incorporation. Our data showed that T-lymphocyte responses are depressed both in P. falciparum (10,500 ñ 2,900 and P. vivax malaria (13,000 ñ 3,300, as compared to that of healthy individuals (27,000 ñ 3,000. Addition of IL-1 partially reserved depression of malaria lymphocytes, but had no effect on normal cells. On the other hand, T-lymphocytes from malaria infected-subjects presented a minimal decrease in proliferation, when cultured in the presence of exogenous PGE2. These data indicate the occurrence of two defects of immunoregulation in malaria: a deficiency of IL-1 production by monocytes/macrophages, and an increased resistance of lymphocytes to the antiproliferative effect of PGE2.

  6. Malaria and Tropical Travel

    Centers for Disease Control (CDC) Podcasts

    2008-05-15

    Malaria is a serious mosquito-borne disease that can lead to death. This podcast discusses malaria risk when traveling to tropical areas, as well as how to protect yourself and your family from malaria infection.  Created: 5/15/2008 by National Center for Zoonotic, Vector-Borne, and Enteric Diseases (NCZVED).   Date Released: 5/29/2008.

  7. Aquaporins in desert rodent physiology.

    Science.gov (United States)

    Pannabecker, Thomas L

    2015-08-01

    Desert rodents face a sizeable challenge in maintaining salt and water homeostasis due to their life in an arid environment. A number of their organ systems exhibit functional characteristics that limit water loss above that which occurs in non-desert species under similar conditions. These systems include renal, pulmonary, gastrointestinal, nasal, and skin epithelia. The desert rodent kidney preserves body water by producing a highly concentrated urine that reaches a maximum osmolality nearly three times that of the common laboratory rat. The precise mechanism by which urine is concentrated in any mammal is unknown. Insights into the process may be more apparent in species that produce highly concentrated urine. Aquaporin water channels play a fundamental role in water transport in several desert rodent organ systems. The role of aquaporins in facilitating highly effective water preservation in desert rodents is only beginning to be explored. The organ systems of desert rodents and their associated AQPs are described.

  8. Genetically-modified mosquitoes for malaria control: requirements to be considered before field releases

    NARCIS (Netherlands)

    Touré, Y.T.; Knols, B.G.J.

    2006-01-01

    The technical feasibility of the development of transgenic mosquitoes highly refractory to (rodent) malaria parasites has been demonstrated in the laboratory. Following this proof of principle, genetic control of vectors could have an important role to play in the interruption of transmission of hum

  9. Randomized comparison of the efficacies and tolerabilities of three artemisinin-based combination treatments for children with acute Plasmodium falciparum malaria in the Democratic Republic of the Congo.

    Science.gov (United States)

    Onyamboko, M A; Fanello, C I; Wongsaen, K; Tarning, J; Cheah, P Y; Tshefu, K A; Dondorp, A M; Nosten, F; White, N J; Day, N P J

    2014-09-01

    An open-label, randomized controlled trial was carried out in 2011-2012 in the Democratic Republic of the Congo to test the efficacy, safety, and tolerability of the artemisinin-based combination treatments dihydroartemisinin-piperaquine, amodiaquine-artesunate, and artemether-lumefantrine. Six hundred eighty-four children aged 3 to 59 months with uncomplicated Plasmodium falciparum malaria were randomly allocated to each study arm. Children were hospitalized for 3 days, given supervised treatment, and followed up weekly for 42 days. All regimens were well tolerated and rapidly effective. The median parasitemia clearance half-life was 2.2 h, and half-lives were similar between arms (P=0.19). The PCR-uncorrected cure rates by day 42 were 73.0% for amodiaquine-artesunate, 70.2% for artemether-lumefantrine, and 86.3% for dihydroartemisinin-piperaquine (P=0.001). Early treatment failure occurred in three patients (0.5%), one in each arm. The PCR-corrected cure rates were 93.4% for amodiaquine-artesunate, 92.7% for artemether-lumefantrine, and 94.3% for dihydroartemisinin-piperaquine (P=0.78). The last provided a longer posttreatment prophylactic effect than did the other two treatments. The day 7 plasma concentration of piperaquine was below 30 ng/ml in 47% of the children treated with dihydroartemisinin-piperaquine, and the day 7 lumefantrine concentration was below 280 ng/ml in 37.0% of children who received artemether-lumefantrine. Thus, although cure rates were all satisfactory, they could be improved by increasing the dose. (This study has been registered with the International Standard Randomized Controlled Trial Number Register [www.isrctn.org] under registration no. ISRCTN20984426.).

  10. Anopheles gambiae immune responses to human and rodent Plasmodium parasite species.

    OpenAIRE

    Yuemei Dong; Ruth Aguilar; Zhiyong Xi; Emma Warr; Emmanuel Mongin; George Dimopoulos

    2006-01-01

    Transmission of malaria is dependent on the successful completion of the Plasmodium lifecycle in the Anopheles vector. Major obstacles are encountered in the midgut tissue, where most parasites are killed by the mosquito's immune system. In the present study, DNA microarray analyses have been used to compare Anopheles gambiae responses to invasion of the midgut epithelium by the ookinete stage of the human pathogen Plasmodium falciparum and the rodent experimental model pathogen P. berghei. I...

  11. Lymphocyte response to purified Plasmodium falciparum antigens during and after malaria

    DEFF Research Database (Denmark)

    Bygbjerg, I C; Jepsen, S; Theander, T G

    1986-01-01

    The peripheral blood lymphocyte response to affinity purified soluble Plasmodium falciparum antigens from in vitro cultures was studied in seven patients with acute falciparum malaria, on eight occasions, and in 15 persons having had malaria, at various times post infection, on 24 occasions. During...

  12. Circulating epstein-barr virus in children living in malaria-endemic areas

    DEFF Research Database (Denmark)

    Rasti, N; Falk, K I; Donati, D;

    2005-01-01

    Children living in malaria-endemic regions have high incidence of Burkitt's lymphoma (BL), the aetiology of which involves Plasmodium falciparum malaria and Epstein-Barr virus (EBV) infections. Acute malarial infection impairs the EBV-specific immune responses with the consequent increase...

  13. Elevated plasma urokinase receptor predicts low birth weight in maternal malaria

    DEFF Research Database (Denmark)

    Ostrowski, S R; Shulman, C E; Peshu, N

    2007-01-01

    The blood level of soluble urokinase receptor (suPAR) is increased and associated with a poor clinical or fatal outcome in children with acute malaria. This study hypothesized that the suPAR level would be associated with foetal outcome in maternal malaria. suPAR was measured by ELISA in maternal...

  14. Inhibition by cyclosporin A of rodent malaria in vivo and human malaria in vitro.

    Science.gov (United States)

    Nickell, S P; Scheibel, L W; Cole, G A

    1982-01-01

    The development and course of normally lethal parasitemias in mice inoculated intraperitoneally with erythrocytic stages of Plasmodium yoelii or Plasmodium berghei were markedly affected by treatment with the antilymphoid drug cyclosporin A (CS-A). When the first of four daily subcutaneous 25-mg/kg doses of CS-A was given at the time of parasite inoculation, patent infections failed to develop. If begun up to 5 days earlier, this same treatment regimen prolonged the prepatent period, attenuated parasitemia, and reduced mortality. In mice with patient infections, two consecutive daily 25-mg/kg doses of CS-A were sufficient to terminate parasitemias which, after several days, reappeared but were self-limiting. This pattern of apparent cure followed by transient recrudescence remained unaltered even when daily treatment with the same drug dose was continued for 3 weeks. Recrudescence was associated with the emergence of parasite populations that were relatively resistant to CS-A and, in the case of P. yoelii, of reduced virulence. In more limited experiments, CS-A was found to be active in vitro against erythrocytic stages of the human malarial parasite palsmodium falciparum. Depending on the concentration of drug in the culture medium, parasite growth was either prevented or inhibited. PMID:6752020

  15. Pilocarpine-induced seizures in rodents--17 years on.

    Science.gov (United States)

    Turski, W A

    2000-01-01

    In 1983, we reported that intracerebral or systemic administration of cholinergic agents produced seizures and seizure-related brain damage in rodents. During the following 17 years, seizures induced by cholinomimetic drugs became a popular model of epilepsy. Seizures can by produced by cholinergic agonists acting directly at muscarinic receptors or by drugs enhancing cholinergic transmission due to the inhibition of acetylcholinesterase activity. Status epilepticus evoked by pilocarpine in rodents triggers long-lasting changes which can be described as: (I) acute-onset seizures lasting for several hours, (II) a silent period characterized by normalization of electroencephalographic patterns lasting for days, and (III) spontaneous recurrent seizures lasting for life. Therefore, seizures induced by cholinomimetics in rodents are of value for studies of basic mechanisms of epileptogenesis and action of antiepileptic drugs.

  16. Oculoscopy in Rabbits and Rodents.

    Science.gov (United States)

    Jekl, Vladimir; Hauptman, Karel; Knotek, Zdenek

    2015-09-01

    Ophthalmic diseases are common in rabbits and rodents. Fast and definitive diagnosis is imperative for successful treatment of ocular diseases. Ophthalmic examination in rabbits and rodents can be challenging. Oculoscopy offers great magnification for the examination of the ocular structures in such animals, including the evaluation of cornea, anterior eye chamber, limbus, iris, lens, and retina. To date, oculoscopy has been described only sporadically and/or under experimental conditions. This article describes the oculoscopy technique, normal and abnormal ocular findings, and the most common eye disorders diagnosed with the aid of endoscopy in rabbits and rodents.

  17. Malaria, malnutrition, and birthweight

    DEFF Research Database (Denmark)

    Cates, Jordan E.; Unger, Holger W.; Briand, Valerie

    2017-01-01

    were identified by the Maternal Malaria and Malnutrition (M3) initiative using a convenience sampling approach and were eligible for pooling given adequate ethical approval and availability of essential variables. Study-specific adjusted effect estimates were calculated using inverse probability...... be multiplicative interaction between malaria infection at enrollment and low MUAC within studies conducted in Africa; however, this finding was not consistent on the additive scale, when accounting for multiple comparisons, or when using other definitions of malaria and malnutrition. The major limitations...... of the study included availability of only 2 cross-sectional measurements of malaria and the limited availability of ultrasound-based pregnancy dating to assess impacts on preterm birth and fetal growth in all studies.  Conclusions : Pregnant women with malnutrition and malaria infection are at increased risk...

  18. Rapid Diagnosis of Malaria

    Directory of Open Access Journals (Sweden)

    Clinton K. Murray

    2009-01-01

    Full Text Available Malaria's global impact is expansive and includes the extremes of the healthcare system ranging from international travelers returning to nonendemic regions with tertiary referral medical care to residents in hyperendemic regions without access to medical care. Implementation of prompt and accurate diagnosis is needed to curb the expanding global impact of malaria associated with ever-increasing antimalarial drug resistance. Traditionally, malaria is diagnosed using clinical criteria and/or light microscopy even though both strategies are clearly inadequate in many healthcare settings. Hand held immunochromatographic rapid diagnostic tests (RDTs have been recognized as an ideal alternative method for diagnosing malaria. Numerous malaria RDTs have been developed and are widely available; however, an assortment of issues related to these products have become apparent. This review provides a summary of RDT including effectiveness and strategies to select the ideal RDT in varying healthcare settings.

  19. Rodent Control: Seal Up! Trap Up! Clean Up!

    Science.gov (United States)

    ... rodent food sources and nesting sites... Diseases from rodents Diseases directly transmitted by rodents Diseases indirectly transmitted by rodents Cleaning up after rodents Take precautions before and during clean up of ...

  20. Inhibition of Malaria Infection in Transgenic Anopheline Mosquitoes Lacking Salivary Gland Cells.

    Science.gov (United States)

    Yamamoto, Daisuke S; Sumitani, Megumi; Kasashima, Katsumi; Sezutsu, Hideki; Matsuoka, Hiroyuki

    2016-09-01

    Malaria is an important global public health challenge, and is transmitted by anopheline mosquitoes during blood feeding. Mosquito vector control is one of the most effective methods to control malaria, and population replacement with genetically engineered mosquitoes to block its transmission is expected to become a new vector control strategy. The salivary glands are an effective target tissue for the expression of molecules that kill or inactivate malaria parasites. Moreover, salivary gland cells express a large number of molecules that facilitate blood feeding and parasite transmission to hosts. In the present study, we adapted a functional deficiency system in specific tissues by inducing cell death using the mouse Bcl-2-associated X protein (Bax) to the Asian malaria vector mosquito, Anopheles stephensi. We applied this technique to salivary gland cells, and produced a transgenic strain containing extremely low amounts of saliva. Although probing times for feeding on mice were longer in transgenic mosquitoes than in wild-type mosquitoes, transgenic mosquitoes still successfully ingested blood. Transgenic mosquitoes also exhibited a significant reduction in oocyst formation in the midgut in a rodent malaria model. These results indicate that mosquito saliva plays an important role in malaria infection in the midgut of anopheline mosquitoes. The dysfunction in the salivary glands enabled the inhibition of malaria transmission from hosts to mosquito midguts. Therefore, salivary components have potential in the development of new drugs or genetically engineered mosquitoes for malaria control.

  1. Enhanced transmission of malaria parasites to mosquitoes in a murine model of type 2 diabetes.

    Science.gov (United States)

    Pakpour, Nazzy; Cheung, Kong Wai; Luckhart, Shirley

    2016-04-21

    More than half of the world's population is at risk of malaria and simultaneously, many malaria-endemic regions are facing dramatic increases in the prevalence of type 2 diabetes. Studies in murine malaria models have examined the impact of malaria infection on type 2 diabetes pathology, it remains unclear how this chronic metabolic disorder impacts the transmission of malaria. In this report, the ability type 2 diabetic rodents infected with malaria to transmit parasites to Anopheles stephensi mosquitoes is quantified. The infection prevalence and intensity of An. stephensi mosquitoes that fed upon control or type 2 diabetic C57BL/6 db/db mice infected with either lethal Plasmodium berghei NK65 or non-lethal Plasmodium yoelii 17XNL murine malaria strains were determined. Daily parasitaemias were also recorded. A higher percentage of mosquitoes (87.5 vs 61.5 % for P. yoelii and 76.9 vs 50 % for P. berghei) became infected following blood feeding on Plasmodium-infected type 2 diabetic mice compared to mosquitoes that fed on infected control animals, despite no significant differences in circulating gametocyte levels. These results suggest that type 2 diabetic mice infected with malaria are more efficient at infecting mosquitoes, raising the question of whether a similar synergy exists in humans.

  2. Inhibition of Malaria Infection in Transgenic Anopheline Mosquitoes Lacking Salivary Gland Cells.

    Directory of Open Access Journals (Sweden)

    Daisuke S Yamamoto

    2016-09-01

    Full Text Available Malaria is an important global public health challenge, and is transmitted by anopheline mosquitoes during blood feeding. Mosquito vector control is one of the most effective methods to control malaria, and population replacement with genetically engineered mosquitoes to block its transmission is expected to become a new vector control strategy. The salivary glands are an effective target tissue for the expression of molecules that kill or inactivate malaria parasites. Moreover, salivary gland cells express a large number of molecules that facilitate blood feeding and parasite transmission to hosts. In the present study, we adapted a functional deficiency system in specific tissues by inducing cell death using the mouse Bcl-2-associated X protein (Bax to the Asian malaria vector mosquito, Anopheles stephensi. We applied this technique to salivary gland cells, and produced a transgenic strain containing extremely low amounts of saliva. Although probing times for feeding on mice were longer in transgenic mosquitoes than in wild-type mosquitoes, transgenic mosquitoes still successfully ingested blood. Transgenic mosquitoes also exhibited a significant reduction in oocyst formation in the midgut in a rodent malaria model. These results indicate that mosquito saliva plays an important role in malaria infection in the midgut of anopheline mosquitoes. The dysfunction in the salivary glands enabled the inhibition of malaria transmission from hosts to mosquito midguts. Therefore, salivary components have potential in the development of new drugs or genetically engineered mosquitoes for malaria control.

  3. The role of cytokines in Plasmodium vivax malaria

    Directory of Open Access Journals (Sweden)

    K. N. Mendis

    1992-01-01

    Full Text Available The cytokine tumor necrosis factor and other as yet unidentified factor(s which together mediate the killing of intraerythrocytic malaria parasites are transiently elevated in sera during paroxysms in human Plasmodium vivax infections in non-immunes. These factors which included TNF and parasite killing factor(s are associated with the clinical disease in malaria to the extent that their transient presence in infection sera coincided with paroxysms, the most pronounced clinical disturbances of P. vivax malaria and secondly because their levels were markedly lower in paroxysm sera of semi-immune patients who were resident of an endemic area. Further, a close parallel was obtained between serum TFN levels and changes in body temperature that occur during a P. vivax paroxysm in non-immune patients, suggesting a causative role for TNF in the fever in malaria. P. vivax rarely if ever cause complicated clinical syndromes. Nevertheles serum TFN levels reached in acutely ill P. vivax patients were as high as in patients suffering from cerebral complications of P. falciparum malaria as reported in studies from the Gambia. Cytokine profiles and other changes accompanying clinical disease in P. vivax and P. falciparum malaria are compared in this paper with a view to discussing the potential role of cytokines in the causation of disease in malaria.

  4. A nice book on Italian rodents

    OpenAIRE

    Bellavere C

    2008-01-01

    A recent book on the Italian rodents is presented. The book treats the ecology of rodents as well as more applied topics like the impact of rodents on human activities and the management and control of rodents populations. Written in Italian.

  5. Rodent empathy and affective neuroscience.

    Science.gov (United States)

    Panksepp, Jules B; Lahvis, Garet P

    2011-10-01

    In the past few years, several experimental studies have suggested that empathy occurs in the social lives of rodents. Thus, rodent behavioral models can now be developed to elucidate the mechanistic substrates of empathy at levels that have heretofore been unavailable. For example, the finding that mice from certain inbred strains express behavioral and physiological responses to conspecific distress, while others do not, underscores that the genetic underpinnings of empathy are specifiable and that they could be harnessed to develop new therapies for human psychosocial impairments. However, the advent of rodent models of empathy is met at the outset with a number of theoretical and semantic problems that are similar to those previously confronted by studies of empathy in humans. The distinct underlying components of empathy must be differentiated from one another and from lay usage of the term. The primary goal of this paper is to review a set of seminal studies that are directly relevant to developing a concept of empathy in rodents. We first consider some of the psychological phenomena that have been associated with empathy, and within this context, we consider the component processes, or endophenotypes of rodent empathy. We then review a series of recent experimental studies that demonstrate the capability of rodents to detect and respond to the affective state of their social partners. We focus primarily on experiments that examine how rodents share affective experiences of fear, but we also highlight how similar types of experimental paradigms can be utilized to evaluate the possibility that rodents share positive affective experiences. Taken together, these studies were inspired by Jaak Panksepp's theory that all mammals are capable of felt affective experiences.

  6. Neuroimaging findings in children with retinopathy-confirmed cerebral malaria

    Energy Technology Data Exchange (ETDEWEB)

    Potchen, Michael J. [Michigan State University, Department of Radiology, 184 Radiology Building, East Lansing, MI 48824-1303 (United States)], E-mail: mjp@rad.msu.edu; Birbeck, Gretchen L. [Michigan State University, International Neurologic and Psychiatric Epidemiology Program, 324 West Fee Hall, East Lansing, MI 48824 (United States)], E-mail: Gretchen.Birbeck@ht.msu.edu; DeMarco, J. Kevin [Michigan State University, Department of Radiology, 184 Radiology Building, East Lansing, MI 48824-1303 (United States)], E-mail: jkd@rad.msu.edu; Kampondeni, Sam D. [University of Malawi, Department of Radiology, Queen Elizabeth Central Hospital, Blantyre (Malawi)], E-mail: kamponde@msu.edu; Beare, Nicholas [St. Paul' s Eye Unit, Royal Liverpool University Hospital, Prescot Street, Liverpool L7 8XP (United Kingdom)], E-mail: nbeare@btinternet.com; Molyneux, Malcolm E. [Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine (Malawi); School of Tropical Medicine, University of Liverpool, Liverpool (United Kingdom)], E-mail: mmolyneux999@google.com; Taylor, Terrie E. [Michigan State University, College of Osteopathic Medicine, B309-B West Fee Hall, East Lansing, MI 48824 (United States); University of Malawi, College of Medicine, Blantyre Malaria Project, Blantyre (Malawi)], E-mail: taylort@msu.edu

    2010-04-15

    Purpose: To describe brain CT findings in retinopathy-confirmed, paediatric cerebral malaria. Materials and methods: In this outcomes study of paediatric cerebral malaria, a subset of children with protracted coma during initial presentation was scanned acutely. Survivors experiencing adverse neurological outcomes also underwent a head CT. All children had ophthalmological examination to confirm the presence of the retinopathy specific for cerebral malaria. Independent interpretation of CT images was provided by two neuroradiologists. Results: Acute brain CT findings in three children included diffuse oedema with obstructive hydrocephalus (2), acute cerebral infarctions in multiple large vessel distributions with secondary oedema and herniation (1), and oedema of thalamic grey matter (1). One child who was reportedly normal prior to admission had parenchymal atrophy suggestive of pre-existing CNS injury. Among 56 survivors (9-84 months old), 15 had adverse neurologic outcomes-11/15 had a follow-up head CT, 3/15 died and 1/15 refused CT. Follow-up head CTs obtained 7-18 months after the acute infection revealed focal and multifocal lobar atrophy correlating to regions affected by focal seizures during the acute infection (5/11). Other findings were communicating hydrocephalus (2/11), vermian atrophy (1/11) and normal studies (3/11). Conclusions: The identification of pre-existing imaging abnormalities in acute cerebral malaria suggests that population-based studies are required to establish the rate and nature of incidental imaging abnormalities in Malawi. Children with focal seizures during acute cerebral malaria developed focal cortical atrophy in these regions at follow-up. Longitudinal studies are needed to further elucidate mechanisms of CNS injury and death in this common fatal disease.

  7. [Malaria in Algerian Sahara].

    Science.gov (United States)

    Hammadi, D; Boubidi, S C; Chaib, S E; Saber, A; Khechache, Y; Gasmi, M; Harrat, Z

    2009-08-01

    Thanks to the malaria eradication campaign launched in Algeria in 1968, the number of malaria cases fell down significantly from 95,424 cases in 1960 to 30 cases in 1978. At that time the northern part of the country was declared free of Plasmodium falciparum. Only few cases belonging to P. vivax persisted in residual foci in the middle part of the country. In the beginning of the eighties, the south of the country was marked by an increase of imported malaria cases. The resurgence of the disease in the oases coincided with the opening of the Trans-Saharan road and the booming trade with the neighbouring southern countries. Several authors insisted on the risk of introduction of malaria or its exotic potential vectors in Algeria via this new road. Now, the totality of malaria autochthonous cases in Algeria are located in the south of the country where 300 cases were declared during the period (1980-2007). The recent outbreak recorded in 2007 at the borders with Mall and the introduction of Anopheles gambiae into the Algerian territory show the vulnerability of this area to malaria which is probably emphasized by the local environmental changes. The authors assess the evolution of malaria in the Sahara region and draw up the distribution of the anopheles in this area.

  8. MALARIA IN CHILDREN

    Directory of Open Access Journals (Sweden)

    Richard-Fabian Schumacher

    2012-01-01

    Full Text Available

    This review is focused on childhood specific aspects of malaria, especially in resource-poor settings. We summarise the actual knowledge in the field of epidemiology, clinical presentation, diagnosis, management and prevention.

    These aspects are important as malaria is responsible for almost a quarter of all child death in sub-Saharan Africa. Malaria control is thus one key intervention to reduce childhood mortality, especially as malaria is also an important risk factor for other severe infections, namely bacteraemia.

    In children symptoms are more varied and often mimic other common childhood illness, particularly gastroenteritis, meningitis/encephalitis, or pneumonia. Fever is the key symptom, but the characteristic regular tertian and quartan patterns are rarely observed. There are no pathognomonic features for severe malaria in this age group. The well known clinical (fever, impaired consciousness, seizures, vomiting, respiratory distress and laboratory (severe anaemia, thrombocytopenia, hypoglycaemia, metabolic acidosis, and hyperlactataemia features of severe falciparum malaria in children, are equally typical for severe sepsis.

    Appropriate therapy (considering species, resistance patterns and individual patient factors – possibly a drug combination of an artemisinin derivative with a long-acting antimalarial drug - reduces treatment duration to only three days and should be urgently started.

    While waiting for the results of ongoing vaccine trials, all effort should be made to better implement other malaria-control measures like the use of treated bed-nets and new chemoprophylaxis regimens.

  9. MALARIA IN CHILDREN

    Directory of Open Access Journals (Sweden)

    Richard-Fabian Schumacher

    2012-11-01

    Full Text Available This review is focused on childhood specific aspects of malaria, especially in resource-poor settings. We summarise the actual knowledge in the field of epidemiology, clinical presentation, diagnosis, management and prevention. These aspects are important as malaria is responsible for almost a quarter of all child death in sub-Saharan Africa. Malaria control is thus one key intervention to reduce childhood mortality, especially as malaria is also an important risk factor for other severe infections, namely bacteraemia. In children symptoms are more varied and often mimic other common childhood illness, particularly gastroenteritis, meningitis/encephalitis, or pneumonia. Fever is the key symptom, but the characteristic regular tertian and quartan patterns are rarely observed. There are no pathognomonic features for severe malaria in this age group. The well known clinical (fever, impaired consciousness, seizures, vomiting, respiratory distress and laboratory (severe anaemia, thrombocytopenia, hypoglycaemia, metabolic acidosis, and hyperlactataemia features of severe falciparum malaria in children, are equally typical for severe sepsis. Appropriate therapy (considering species, resistance patterns and individual patient factors – possibly a drug combination of an artemisinin derivative with a long-acting antimalarial drug - reduces treatment duration to only three days and should be urgently started. While waiting for the results of ongoing vaccine trials, all effort should be made to better implement other malaria-control measures like the use of treated bed-nets and new chemoprophylaxis regimens.

  10. Cerebral malaria is associated with low levels of circulating endothelial progenitor cells in African children.

    Science.gov (United States)

    Gyan, Ben; Goka, Bamenla Quarm; Adjei, George O; Tetteh, John K A; Kusi, Kwadwo Asamoah; Aikins, Anastasia; Dodoo, Daniel; Lesser, Martin L; Sison, Cristina P; Das, Sanchita; Howard, Marion E; Milbank, Elizabeth; Fischer, Kimberly; Rafii, Shahin; Jin, David; Golightly, Linnie M

    2009-04-01

    Damage to the cerebral microvasculature is a feature of cerebral malaria. Circulating endothelial progenitor cells are needed for microvascular repair. Based on this knowledge, we hypothesized that the failure to mobilize sufficient circulating endothelial progenitor cells to the cerebral microvasculature is a pathophysiologic feature of cerebral malaria. To test this hypothesis, we compared peripheral blood levels of CD34 (+)/VEGFR2(+) and CD34 (+)/CD133(+) cells and plasma levels of the chemokine stromal cell-derived growth factor 1 (SDF-1) in 214 children in Accra, Ghana. Children with cerebral malaria had lower levels of CD34 (+)/VEGFR2(+) and CD34 (+)/CD133(+) cells compared with those with uncomplicated malaria, asymptomatic parasitemia, or healthy controls. SDF-1 levels were higher in children with acute malaria compared with healthy controls. Together, these results uncover a potentially novel role for endothelial progenitor cell mobilization in the pathophysiology of cerebral malaria.

  11. Malaria prevention in travelers.

    Science.gov (United States)

    Genton, Blaise; D'Acremont, Valérie

    2012-09-01

    A common approach to malaria prevention is to follow the "A, B, C, D" rule: Awareness of risk, Bite avoidance, Compliance with chemoprophylaxis, and prompt Diagnosis in case of fever. The risk of acquiring malaria depends on the length and intensity of exposure; the risk of developing severe disease is primarily determined by the health status of the traveler. These parameters need to be assessed before recommending chemoprophylaxis and/or stand-by emergency treatment. This review discusses the different strategies and drug options available for the prevention of malaria during and post travel.

  12. Imported submicroscopic malaria in Madrid

    Directory of Open Access Journals (Sweden)

    Ramírez-Olivencia Germán

    2012-09-01

    Full Text Available Abstract Background Submicroscopic malaria (SMM can be defined as low-density infections of Plasmodium that are unlikely to be detected by conventional microscopy. Such submicroscopic infections only occasionally cause acute disease, but they are capable of infecting mosquitoes and contributing to transmission. This entity is frequent in endemic countries; however, little is known about imported SMM. The goals of this study were two-fold: a to know the frequency of imported SMM, and b to describe epidemiological, laboratorial and clinical features of imported SMM. Methods A retrospective study based on review of medical records was performed. The study population consisted of patients older than 15 years attended at the Tropical Medicine Unit of Hospital Carlos III, between January 1, 2002 and December 31, 2007. Routinely detection techniques for Plasmodium included Field staining and microscopic examination through thick and thin blood smear. A semi-nested multiplex malaria PCR was used to diagnose or to confirm cases with low parasitaemia. Results SMM was diagnosed in 104 cases, representing 35.5% of all malaria cases. Mean age (IC95% was 40.38 years (37.41-43.34, and sex distribution was similar. Most cases were in immigrants, but some cases were found in travellers. Equatorial Guinea was the main country where infection was acquired (81.7%. Symptoms were present only in 28.8% of all SMM cases, mainly asthenia (73.3% of symptomatic patients, fever (60% and arthromialgias (53.3%. The associated laboratory abnormalities were anaemia (27.9%, leukopaenia (15.4% and thrombopaenia (15.4%. Co-morbidity was described in 75 cases (72.1%. Conclusions Results from this study suggest that imported SMM should be considered in some patients attended at Tropical Medicine Units. Although it is usually asymptomatic, it may be responsible of fever, or laboratory abnormalities in patients coming from endemic areas. The possibility of transmission in SMM has

  13. HLA and malaria in four colombian ethnic groups

    Directory of Open Access Journals (Sweden)

    Marcos Restrepo

    1988-10-01

    Full Text Available HLA antigens and their relationship with malaria infection were studied in four different ethnic groups in Colombia (South America: two groups of indians (Kunas and Katios, one of negroes and a group of mixed ancestry. A total of 965 persons were studied, 415 with malaria and 550 as controls. HLA-A,B, and C antigen frequencies in the four groups are reported. The association of each HLA antigen with malaria infection due to P. vivax and to P. falciparum was evaluated. Negroes, Kunas and Katios indians variously lack from 6 to 9 of the HLA antigens found in the mixed group. In the designated ethnic groups, antigens B5, B13, B15, Cw2 and Cw4 showed borderline association with malaria infection. However, in the mixed ethnic group, statistically significant associations were found with malaria infection and the presence of A9, Aw19, B17, B35, and Z98 (a B21-B45: crossreacting determinant with few differences when P. vivax infection and P. falciparum infection were considered individually. This finding may represent a lack of general resistance to malaria in the group that harbors antigens of Caucasian origin. These individuals have been in direct and permanent contact with malaria only in the past 65 years. In contrast, indians, both Kunas and Katios, and Negroes have lived for centuries in malaria endemic areas, and it is possible that a natural selection system has developed through which only those individuals able to initiate an acute immune response to malaria have survived.

  14. Adjuvants for malaria vaccines.

    Science.gov (United States)

    Coler, R N; Carter, D; Friede, M; Reed, S G

    2009-09-01

    There is a renewed enthusiasm about subunit vaccines for malaria coincident with the formation of new alliances and partnerships raising international public awareness, attracting increased resources and the re-focusing of research programs on adjuvant development for infectious disease vaccines. It is generally accepted that subunit vaccines for malaria will require adjuvants to induce protective immune responses, and availability of suitable adjuvants has in the past been a barrier to the development of malaria vaccines. Several novel adjuvants are now in licensed products or in late stage clinical development, while several others are in the earlier development pipeline. Successful vaccine development requires knowing which adjuvants to use and knowing how to formulate adjuvants and antigens to achieve stable, safe, and immunogenic vaccines. For the majority of vaccine researchers this information is not readily available, nor is access to well-characterized adjuvants. In this minireview, we outline the current state of adjuvant research and development as it pertains to effective malaria vaccines.

  15. Malaria prevention and treatment

    African Journals Online (AJOL)

    to allow prompt and accurate treatment of malaria in areas out of .... Other psychiatric problems ... If possible blood smears should be performed if a reliable laboratory is available. ... If any of the above signs are present, this is an emergency.

  16. Bioinformatics approaches to malaria

    DEFF Research Database (Denmark)

    Hansen, Daniel Aaen

    Malaria is a life threatening disease found in tropical and subtropical regions of the world. Each year it kills 781 000 individuals; most of them are children under the age of five in sub-Saharan Africa. The most severe form of malaria in humans is caused by the parasite Plasmodium falciparum......, which is the subject of the first part of this thesis. The PfEMP1 protein which is encoded by the highly variablevargene family is important in the pathogenesis and immune evasion of malaria parasites. We analyzed and classified these genes based on the upstream sequence in seven......Plasmodium falciparumclones. We show that the amount of nucleotide diversity is just as big within each clone as it is between the clones. DNA methylation is an important epigenetic mark in many eukaryotic species. We are studying DNA methylation in the malaria parasitePlasmodium falciparum. The work is still in progress...

  17. Malaria Genome Sequencing Project

    Science.gov (United States)

    2004-01-01

    million cases and up to 2.7 million A whole chromosome shotgun sequencing strategy was used to deaths from malaria each year. The mortality levels are...deaths from malaria each year. The mortality levels are greatest in determine the genome sequence of P. falciparum clone 3D7. This sub-Saharan Africa...aminolevulinic acid dehydratase. Cura . Genet. 40, 391-398 (2002). 15. Lasonder, E. et al Analysis of the Plasmodium falciparum proteome by high-accuracy mass

  18. Malaria in Pregnancy

    OpenAIRE

    Apuzzio, Joseph J.; Abdulla Al-Khan; Jesus R. Alvarez

    2005-01-01

    Recently, there has been a resurgence of malaria in densely populated areas of the United States secondary to human migration from endemic areas where factors such as cessation of vector control, vector resistance to insecticides, disease resistance to drugs, environmental changes, political instability, and indifference, have played a role for malaria becoming an overwhelming infection of these tropical underdeveloped countries. It is important for health care providers of gravida to be aler...

  19. Malaria in pregnancy.

    OpenAIRE

    Jesus R. Alvarez; Al-Khan, Abdulla; Apuzzio, Joseph J.

    2005-01-01

    Recently, there has been a resurgence of malaria in densely populated areas of the United States secondary to human migration from endemic areas where factors such as cessation of vector control, vector resistance to insecticides, disease resistance to drugs, environmental changes, political instability, and indifference, have played a role for malaria becoming an overwhelming infection of these tropical underdeveloped countries. It is important for health care providers of gravida to be aler...

  20. Malaria in Pregnancy

    Directory of Open Access Journals (Sweden)

    Jesus R. Alvarez

    2005-01-01

    Full Text Available Recently, there has been a resurgence of malaria in densely populated areas of the United States secondary to human migration from endemic areas where factors such as cessation of vector control, vector resistance to insecticides, disease resistance to drugs, environmental changes, political instability, and indifference, have played a role for malaria becoming an overwhelming infection of these tropical underdeveloped countries. It is important for health care providers of gravida to be alert of the disease and its effects on pregnancy.

  1. Malaria in pregnancy.

    Science.gov (United States)

    Alvarez, Jesus R; Al-Khan, Abdulla; Apuzzio, Joseph J

    2005-12-01

    Recently, there has been a resurgence of malaria in densely populated areas of the United States secondary to human migration from endemic areas where factors such as cessation of vector control, vector resistance to insecticides, disease resistance to drugs, environmental changes, political instability, and indifference, have played a role for malaria becoming an overwhelming infection of these tropical underdeveloped countries. It is important for health care providers of gravida to be alert of the disease and its effects on pregnancy.

  2. Malaria in pregnancy.

    Science.gov (United States)

    Seal, Subrata Lall; Mukhopadhay, Sima; Ganguly, Rajendra Prasad

    2010-08-01

    Malaria during pregnancy is a recognised risk factor for maternal and foetal complications and it is endemic in certain areas of our country. Pregnancy also enhances the severity of malaria particularly with P falciparum infestation. The outcome of effects of malaria in pregnancy on the mother and foetus is studied here. This is a prospective observational study conducted in the department of obstetrics and gynaecology of RG Kar Medical College during the period from 1st January 2001 to 31st December 2006. Forty pregnant women with malaria in pregnancy were studied. Another 40 non- pregnant women during the same period were served as control. The maternal complications were compared with the controls and the outcome of pregnancy was studied. There was statistically significant (p renal failure, hepatic failure, hypoglycaemia, hypotension and death in the pregnant women in comparison to non-pregnant women. P falciparum infection was also more during pregnancy. There was also increased incidence of abqrtion, preterm labour, intra-uterine growth restriction and intra-uterine foetal death. Treatment with antimalarial drugs particularly in cerebral malaria does not give good results as there were 12 maternal deaths in this series. Every attempt should be made to prevent malaria during pregnancy by various measures as it is associated with high maternal morbidity and mortality and adversely affects the neonatal outcome.

  3. Prevalence of congenital malaria among newly born babies at ...

    African Journals Online (AJOL)

    Many pregnant women suffer from severe anaemia, and even death due to acute ... Malaria is one of the ten most common causes of morbidity in the region. ... to decline participation or withdraw from the study at any stage without the fear of ...

  4. Malaria clusters among illegal Chinese immigrants to Europe through Africa.

    Science.gov (United States)

    Bisoffi, Zeno; Matteelli, Alberto; Aquilini, Donatella; Guaraldi, Giovanni; Magnani, Giacomo; Orlando, Giovanna; Gaiera, Giovanni; Jelinek, Tomas; Behrens, Ron H

    2003-09-01

    Between November 2002 and March 2003, 17 cases of malaria (1 fatal) were observed in illegal Chinese immigrants who traveled to Italy through Africa. A further cluster of 12 was reported in August, 2002. Several immigrants traveled by air, making the risk of introducing sudden acute respiratory syndrome a possibility should such illegal immigrations continue.

  5. How benign is benign tertian malaria?

    Directory of Open Access Journals (Sweden)

    Archna Sharma

    2009-06-01

    Full Text Available Objective: This retrospective study was conducted to determine the incidence of variouscomplications of Plasmodium vivax malaria based on review of case records.Methods: The case records of all confirmed cases of malaria over the period of one year (September2005–August 2006 were studied. Complete blood count, peripheral blood findings, liver and kidneyfunctions were reviewed. The results of rapid diagnostic test for malaria (OptiMAL test, DiamedAG, Switzerland were correlated with the peripheral blood smear findings in the patients in whomit was requested. All abnormal results like a positive direct Coomb’s test were noted. Findingswere clinically correlated.Results: There were 265 confirmed cases by peripheral blood examination. Of these 221 were dueto Plasmodium vivax and 41 due to P. falciparum. Two cases had mixed infection and in one casethe species could not be identified as it showed only malarial pigment. The peak incidence ofmalaria was seen in September 2005 and August 2006. The complications in P. vivax werethrombocytopenia, biochemical evidence of hepatic dysfunction, renal damage, positive DCT anddeath due to ARDS. Thrombocytopenia was seen in 213 patients with counts 3 mg/dl with normal liver enzymes. Liver enzymeswere elevated in 60 patients with seven patients showing liver enzymes level, three times the normal.Renal dysfunction was seen in 17 patients with serum creatinine ranging from 1.3–10.65 mg/dl.One patient went into acute renal failure following quinine therapy and showed red cell fragmentsin the peripheral blood. In two children DCT was positive with the peripheral smear showing RBCagglutinates around the parasitised RBC. There were three maternal deaths at about 32 weeksgestation due to ARDS. The peripheral blood smear in these patients showed WBC agglutinates.Conclusion: This paper is presented to highlight that P. vivax malaria though considered to be abenign entity can also have a severe and complicated course

  6. Evidence of endothelial inflammation, T cell activation, and T cell reallocation in uncomplicated Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Elhassan, I M; Hviid, L; Satti, G

    1994-01-01

    To explain the observation that acute Plasmodium falciparum malaria is associated with a transient inability of peripheral blood cells to respond to antigenic stimulation in vitro, we have postulated the disease-induced reallocation of peripheral lymphocytes, possibly by adhesion to inflamed...... endothelium. We measured plasma levels of soluble markers of endothelial inflammation and T cell activation in 32 patients suffering from acute, uncomplication P. falciparum malaria, as well as in 10 healthy, aparasitemic control donors. All donors were residents of a malaria-endemic area of Eastern State...... with the control donors. In addition, we found a disease-induced depletion of T cells with high expression of the LFA-1 antigen, particularly in the CD4+ subset. The results obtained provide further support for the hypothesis of T cell reallocation to inflamed endothelium in acute P. falciparum malaria....

  7. Duration of Acute and Chronic Toxicity Testing in Animals (ICH S4A and S4B)

    DEFF Research Database (Denmark)

    Spindler, Per; Van Cauteren, Herman

    2013-01-01

    To support approval of pharmaceuticals for long term use in humans it is required that product safety is supported by acute and chronic toxicity studies in rodents and non-rodents. The duration of acute toxicity studies (S4A) and chronic rodent studies (S4B) were harmonised between the three ICH ...

  8. KELUHAN DAN KEPATUHAN PENDERITA MALARIA TERHADAP PENGOBATAN MALARIA ARTESUNAT-AMODIAKUIN DI KALIMANTAN DAN SULAWESI

    Directory of Open Access Journals (Sweden)

    Mariana Raini

    2012-07-01

    Full Text Available Drug resistance is one of the global problems, particularly in communicable diseases control including Indonesian malaria elimination program. Since 2004, Artesunate-Amodiaquine (AS+AQ, an Artemisinin based Combination Therapy (ACT, has been used in Indonesia as recommended by the WHO for treatment of acute uncomplicated malaria, replacing of chloroquine resistant antimalarial. Since then, implementation of AS+AQ has never been evaluated. It was reported that AS+AQ coverage was 33,7% because the patients did not comply due to adverse events, and the combination therapy was not a single formulation (fixed-dose. Therefore, there is a need to assess and evaluate the compliance of AS+AQ on subjects malaria treated with AS+AQ at Health Center (Puskesmas sentinel sites in Kalimantan and Sulawesi.  This was a cross-sectional and non intervention observational study. There were 99 malaria subjects participated in this study.  All subjects were treated with 3 days regimen AS+AQ as the national malaria treatment guideline, and they were followed-up on days 3, 7 and 28. Indepth interview was done in several subjects  as informants and staff of puskesmas for knowledge, attitude, practice (KAP of AS+AQ used. Of the 99 malaria subjects evaluated, there were 34 P. falciparum, 36 P. vivax, and 29 mixed infection malaria subjects. Almost all the study subjects (92,9%  completed the therapy. There were 2 subjects withdrawn due to serious adverse event (SAE, 4 subjects were withdrawn because of having severe untolerable adverse events and 1 subject because of lost to follow up. About 84% subjects experienced clinical complaints after AS+AQ administered. Most of the complaints were mild to moderate and tolerable. Overall, the compliance of the 3-day AS+AQ regimen was moderately satisfied. AbstrakResistensi obat merupakan salah satu masalah kesehatan di dunia, khususnya  dalam pengendalian penyakit menular termasuk program pemberantasan malaria di Indonesia

  9. Monkey malaria kills four humans.

    Science.gov (United States)

    Galinski, Mary R; Barnwell, John W

    2009-05-01

    Four human deaths caused by Plasmodium knowlesi, a simian malaria species, are stimulating a surge of public health interest and clinical vigilance in vulnerable areas of Southeast Asia. We, and other colleagues, emphasize that these cases, identified in Malaysia, are a clear warning that health facilities and clinicians must rethink the diagnosis and treatment of malaria cases presumed to be caused by a less virulent human malaria species, Plasmodium malariae.

  10. Fighting malaria with engineered symbiotic bacteria from vector mosquitoes.

    Science.gov (United States)

    Wang, Sibao; Ghosh, Anil K; Bongio, Nicholas; Stebbings, Kevin A; Lampe, David J; Jacobs-Lorena, Marcelo

    2012-07-31

    The most vulnerable stages of Plasmodium development occur in the lumen of the mosquito midgut, a compartment shared with symbiotic bacteria. Here, we describe a strategy that uses symbiotic bacteria to deliver antimalaria effector molecules to the midgut lumen, thus rendering host mosquitoes refractory to malaria infection. The Escherichia coli hemolysin A secretion system was used to promote the secretion of a variety of anti-Plasmodium effector proteins by Pantoea agglomerans, a common mosquito symbiotic bacterium. These engineered P. agglomerans strains inhibited development of the human malaria parasite Plasmodium falciparum and rodent malaria parasite Plasmodium berghei by up to 98%. Significantly, the proportion of mosquitoes carrying parasites (prevalence) decreased by up to 84% for two of the effector molecules, scorpine, a potent antiplasmodial peptide and (EPIP)(4), four copies of Plasmodium enolase-plasminogen interaction peptide that prevents plasminogen binding to the ookinete surface. We demonstrate the use of an engineered symbiotic bacterium to interfere with the development of P. falciparum in the mosquito. These findings provide the foundation for the use of genetically modified symbiotic bacteria as a powerful tool to combat malaria.

  11. Filaria-induced IL-10 suppresses murine cerebral malaria.

    Science.gov (United States)

    Specht, Sabine; Ruiz, Daniel Fernández; Dubben, Bettina; Deininger, Susanne; Hoerauf, Achim

    2010-08-01

    Filarial nematodes achieve long survival in their hosts due to their capacity to modulate immune responses. Therefore, immunomodulation by filarial nematodes may alter responses to concomitant infections such as malaria. Cerebral malaria (CM), a severe complication of Plasmodium falciparum infections, is triggered as a consequence of the immune response developed against malaria parasites. The question arises whether prior infection with helminth parasites is beneficial against CM. In the present work a murine model for subsequent has been used to assess this hypothesis. C57BL/6 mice were infected with the rodent filarial parasite Litomosoides sigmodontis and the murine model parasite for CM, Plasmodium berghei ANKA. Previously filaria-infected C57BL/6 mice showed significantly reduced CM rates. CD8(+) T cell recruitment to the brain, a hallmark for CM development, was reduced in protected mice. Furthermore, in contrast to P. berghei single-infected animals, filaria-infected mice had significantly higher levels of circulating IL-10. The requirement for IL-10 in CM protection was demonstrated by the lack of protection in IL-10 KO mice. This suggests that the anti-inflammatory IL-10 elicited by filarial nematodes is able to suppress the overwhelming inflammatory reaction otherwise triggered against malaria parasites in C57BL/6 mice, preventing full progress to CM.

  12. The Ethics of Rodent Control

    NARCIS (Netherlands)

    Meerburg, B.G.; Brom, F.W.A.; Kijlstra, A.

    2008-01-01

    Because western societies generally see animals as objects of moral concern, demands have been made on the way they are treated, e.g. during animal experimentation. In the case of rodent pests, however, inhumane control methods are often applied. This inconsistency in the human-animal relationship r

  13. Forecasting rodent outbreaks in Africa

    DEFF Research Database (Denmark)

    Leirs, Herwig; Verhagen, Ron; Verheyen, Walter

    1996-01-01

    1. Rainfall data were collated for years preceding historical outbreaks of Mastomys rats in East Africa in order to test the hypothesis that such outbreaks occur after long dry periods. 2. Rodent outbreaks were generally not preceded by long dry periods. 3. Population dynamics of Mastomys natalen...

  14. The Ethics of Rodent Control

    NARCIS (Netherlands)

    Meerburg, B.G.; Brom, F.W.A.; Kijlstra, A.

    2008-01-01

    Because western societies generally see animals as objects of moral concern, demands have been made on the way they are treated, e.g. during animal experimentation. In the case of rodent pests, however, inhumane control methods are often applied. This inconsistency in the human-animal relationship

  15. Forecasting rodent outbreaks in Africa

    DEFF Research Database (Denmark)

    Leirs, Herwig; Verhagen, Ron; Verheyen, Walter

    1996-01-01

    natalensis rats in Tanzania are significantly affected by the distribution of rainfall during the rainy season. 4. All previous rodent outbreaks in Tanzania were preceded by abundant rainfall early in the rainy season, i.e, towards the end of the year. 5. A flow chart is constructed to assess the likelihood...

  16. Towards A Malaria Vaccine?

    Directory of Open Access Journals (Sweden)

    B S GARG

    1990-12-01

    Full Text Available The last few years have seen a marked change in the understanding of malaria mmunology.We have very little knowledge on immunity of Malaria based on experiments in humanbeings due to ethical reasons. Whatsoever our knowledge exists at present is based onexperimentas in mice and monkey. However it is clear that it is sporzoite or merozoitewhich is directly exposed to our immune system in the life cycle of Malaria parasite. On thebasis of human experiments we can draw inference that immunity to malaria is species.specific (on cross immunity, stage specific and strain specific as well acquired in the response to surface antigen and relapsed antigen although the parasite also demonstrates escape machanism to immune system.So the host system kills or elimi nate the parasite by means of (a Antbody to extracell~ular form of parasite with the help of mechanism of Block invasion, Agglutination or opsonization and/or (b Cellular machanism-either by phago-cytosis of parasite or by antibody dependent cellular cytotoxicity ABCC (? or by effects of mediators like tumor necrosis fJ.ctor (TNF in cerebaral malaria or crisis forming factor as found in sudan or by possible role of lysis mechanism.However, inspite of all these theories the parasite has been able to invade the immunesystem by virtue of its intracellular development stage specificity, sequestration in capillaries and also by its unusual characteristics of antigenic diversity and antigenic variation.

  17. 21 CFR 1250.96 - Rodent control.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Rodent control. 1250.96 Section 1250.96 Food and... SANITATION Sanitation Facilities and Conditions on Vessels § 1250.96 Rodent control. Vessels shall be... of rodent control....

  18. Rodent Oncology: Diseases, Diagnostics, and Therapeutics.

    Science.gov (United States)

    Hocker, Samuel E; Eshar, David; Wouda, Raelene M

    2017-01-01

    Cancer incidence in rodent species varies dramatically from a common occurrence in mice and rats to just a limited number of documented cases in chinchillas and degus. This article summarizes common tumors, both benign and malignant, that have been reported to occur in rodents. Outlined are clinical signs, diagnostics, and treatments that have been described for rodents presenting with specific neoplasms.

  19. Placental malaria and lack of prenatal care in an area of unstable malaria transmission in eastern Sudan.

    Science.gov (United States)

    Adam, Ishag; Adamt, Gamal K; Mohmmed, Ahmed A; Salih, Magdi M; Ibrahuim, Salah A; Ryan, C Anthony

    2009-06-01

    A cross-sectional study was conducted in Gadarif Hospital in eastern Sudan to determine the prevalence, and evaluate the risk factors, of placental malaria. Two hundred and thirty-six delivering women were enrolled in the study. Socio-demographic characteristics were gathered through questionnaires. Maternal hemoglobin was measured, ABO blood groups were determined, and placental histological examinations for malaria were performed. The birth weight of the newborn was also recorded. The mean (SD) maternal age was 25.5 (6.0) yr and the mean (SD) hemoglobin was 9.8 (0.9) g/dl. Placental histology showed acute malaria infections in 13 (5.5%) and chronic infections in 5 (2.1%) women; 28 (11.9%) of the placentas revealed past infection and 190 (80.5%) indicated no infection. Lack of prenatal care was significantly associated with placental infections (OR = 12.0, 95% CI = 2.3-16.2; P = 0.003). There was no significant association between placental malaria infections and maternal age, parity, and blood group. Thirty-two (13.5%) of these pregnancy outcomes resulted in low birthweight babies. There was, however, no significant association between placental malaria and low birth weight (OR = 2.0, 95% CI = 0.4-4.1; P = 0.1). Thus, placental malaria infections affect pregnant women in this area of eastern Sudan regardless of their age or parity. Prenatal care should be encouraged to reduce malaria in the area. Much more research regarding malaria and pregnancy is needed.

  20. The impact of endemic and epidemic malaria on the risk of stillbirth in two areas of Tanzania with different malaria transmission patterns

    Directory of Open Access Journals (Sweden)

    Mutabingwa TK

    2006-10-01

    Full Text Available Abstract Background The impact of malaria on the risk of stillbirth is still under debate. The aim of the present analysis was to determine comparative changes in stillbirth prevalence between two areas of Tanzania with different malaria transmission patterns in order to estimate the malaria attributable component. Methods A retrospective analysis was completed of stillbirth differences between primigravidae and multigravidae in relation to malaria cases and transmission patterns for two different areas of Tanzania with a focus on the effects of the El Niño southern climatic oscillation (ENSO. One area, Kagera, experiences outbreaks of malaria, and the other area, Morogoro, is holoendemic. Delivery and malaria data were collected over a six year period from records of the two district hospitals in these locations. Results There was a significantly higher prevalence of low birthweight in primigravidae compared to multigravidae for both data sets. Low birthweight and stillbirth prevalence (17.5% and 4.8% were significantly higher in Kilosa compared to Ndolage (11.9% and 2.4%. There was a significant difference in stillbirth prevalence between Ndolage and Kilosa between malaria seasons (2.4% and 5.6% respectively, p Conclusion Malaria exposure during pregnancy has a delayed effect on birthweight outcomes, but a more acute effect on stillbirth risk.

  1. [Study on malaria vectors in malaria endemic areas of Tibet autonomous region].

    Science.gov (United States)

    Wu, Song; Huang, Fang; Zhou, Shui-Sen; Tang, Lin-Hua

    2012-12-01

    The malaria situation in Tibet has been in an active status and the malaria incidence reached the second in China in 2010. Malaria vector prevention and control is one of the important methods for malaria control, while the malaria vectors are still unknown in Tibet. The author summarized the past researches on malaria vectors in Tibet, so as to provide the evidence for improving malaria control investigation in malaria endemic areas of Tibet, with hopes to provide useful vector message for other researcher.

  2. MIGRATION AND MALARIA IN EUROPE

    Directory of Open Access Journals (Sweden)

    Begoña Monge-Maillo

    2012-03-01

    Full Text Available The proportion of imported malaria cases due to immigrants in Europe has increased during the lasts decades, being the higher rates for those settled immigrants who travel to visit friends and relatives (VFRs at their country of origin. Cases are mainly due to P. falciparum and Sub-Saharan Africa is the most common origin. Clinically, malaria in immigrants is characterized by a mild clinical presentation with even asymptomatic o delayed malaria cases and low parasitemic level. These characteristics may be explained by a semi-immunity acquired after long periods of time exposed to stable transmission of malaria. Malaria cases among immigrants, even those asymptomatic patients with sub-microscopic parasitemia, could increase the risk of transmission and reintroduction of malaria in certain areas with the adequate vectors and climate conditions. Moreover imported malaria cases by immigrants can also play an important role in the non-vectorial transmission out of endemic area, by blood transfusions, organ transplantation or congenital or occupational exposures. Probably, out of endemic areas, screening of malaria among recent arrived immigrants coming from malaria endemic countries should be performed. These aim to reduce the risk of clinical malaria in the individual as well as to prevent autochthonous transmission of malaria in areas where it had been eradicated.

  3. Research toward Malaria Vaccines

    Science.gov (United States)

    Miller, Louis H.; Howard, Russell J.; Carter, Richard; Good, Michael F.; Nussenzweig, Victor; Nussenzweig, Ruth S.

    1986-12-01

    Malaria exacts a toll of disease to people in the Tropics that seems incomprehensible to those only familiar with medicine and human health in the developed world. The methods of molecular biology, immunology, and cell biology are now being used to develop an antimalarial vaccine. The Plasmodium parasites that cause malaria have many stages in their life cycle. Each stage is antigenically distinct and potentially could be interrupted by different vaccines. However, achieving complete protection by vaccination may require a better understanding of the complexities of B- and T-cell priming in natural infections and the development of an appropriate adjuvant for use in humans.

  4. Ophthalmologic identification of cerebral malaria in adults

    Directory of Open Access Journals (Sweden)

    Pedrosa, Catarina Areias

    2015-11-01

    Full Text Available Objective: To report the clinical presentation of malarial retinopathy in an adult, emphasizing the importance of this diagnosis for the clinical suspicion and prognosis of cerebral malaria. Methods: A 39-year-old caucasian man presented with hemolytic anemia, thrombocytopenia, acidemia and acute renal failure, developing severe encephalopathy. The diagnosis of malaria was done and after systemic stabilization, the patient noticed a central scotoma in the left eye. Ophthalmological examination revealed retinal features of malarial retinopathy. Results: At one-month follow-up, the patient had improved his systemic condition and the left eye scotoma had disappeared. Visual acuity was 20/20 in both eyes and on examination almost all lesions had regressed. Conclusion: Malarial retinopathy is a diagnostic factor and a prognosis indicator of severe infection, usually with brain involvement. The knowledge of the ophthalmological features associated with severe malaria, which is more frequent in children but can also occur in adults, becomes imperative in order to reduce the risk of neurologic sequelae and associated mortality.

  5. Pathomorphological effects of Alloxan induced acute hypoglycaemia ...

    African Journals Online (AJOL)

    Masood Saleem Mir

    2013-04-09

    Apr 9, 2013 ... humans and rodents under different glycemic conditions have shown that acute ..... sium (K+) leakage, all of which are indices of plasma membrane .... V. Nutritional and hypoglycemic effect of fruit pulp of Annona squamosa in ...

  6. Determining utility values related to malaria and malaria chemoprophylaxis

    Directory of Open Access Journals (Sweden)

    Coyle Doug

    2010-04-01

    Full Text Available Abstract Background Chemoprophylaxis for travellers' malaria is problematic. Decision modeling may help determine optimal prevention strategies for travellers' malaria. Such models can fully assess effect of drug use and disease on quality of life, and help travellers make informed values based decisions. Such models require utility values reflecting societal preferences over different health states of relevance. To date, there are no published utility values relating to clinical malaria or chemoprophylaxis adverse events. Methods Utility estimates for health states related to falciparum malaria, sequelae and drug-related adverse events were obtained using a self-administered visual analogue scale in 20 individuals. Utility values for health states related to clinical malaria were obtained from a survey of 11 malaria experts questioned about length of hospital stay or equivalent disability with simple and severe travellers' malaria. Results The general public (potential travellers, were more tolerant of taking prophylaxis if associated with no or mild AEs and least tolerant of mild sequelae from malaria and severe drug related events. The rating value reported for taking no prophylaxis was quite variable. Tropical medicine specialists estimated a mean hospital stay 3.23 days (range 0.5-4.5 days for simple and 6.36 days (range 4.5 - 7 days for severe malaria. Conclusions This study provides a benchmark for important utility value estimates for modeling malaria and drug-related outcomes in non-immune travellers.

  7. Visualization of Malaria Parasites in the Skin Using the Luciferase Transgenic Parasite, Plasmodium berghei

    OpenAIRE

    Matsuoka, Hiroyuki; TOMITA, HIROYUKI; Hattori, Ryuta; Arai,Meiji; Hirai, Makoto

    2014-01-01

    We produced a transgenic rodent malaria parasite (Plasmodium berghei) that contained the luciferase gene under a promoter region of elongation factor-1α. These transgenic (TG) parasites expressed luciferase in all stages of their life cycle, as previously reported. However, we were the first to succeed in observing sporozoites as a mass in mouse skin following their deposition by the probing of infective mosquitoes. Our transgenic parasites may have emitted stronger bioluminescence than previ...

  8. A novel FIKK kinase regulates the development of mosquito and liver stages of the malaria

    OpenAIRE

    Jaijyan, Dabbu Kumar; Verma, Praveen Kumar; Singh, Agam Prasad

    2016-01-01

    Protein phosphorylation is the most important post-translational event in the regulation of various essential signaling pathways in a cell. Here, we show the functional characterization of a FIKK family protein kinase of the rodent malaria parasite (PbMLFK), which is expressed only in mosquito and liver stages and contains two functional C-terminal PEXEL motifs. We demonstrate that this protein plays a role in mosquito and liver stages of parasite growth. The oocysts of PbMLFK-deficient paras...

  9. Coadaptation and malaria control

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Tosta

    2007-06-01

    Full Text Available Malaria emerges from a disequilibrium of the system 'human-plasmodium-mosquito' (HPM. If the equilibrium is maintained, malaria does not ensue and the result is asymptomatic plasmodium infection. The relationships among the components of the system involve coadaptive linkages that lead to equilibrium. A vast body of evidence supports this assumption, including the strategies involved in the relationships between plasmodium and human and mosquito immune systems, and the emergence of resistance of plasmodia to antimalarial drugs and of mosquitoes to insecticides. Coadaptive strategies for malaria control are based on the following principles: (1 the system HPM is composed of three highly complex and dynamic components, whose interplay involves coadaptive linkages that tend to maintain the equilibrium of the system; (2 human and mosquito immune systems play a central role in the coadaptive interplay with plasmodium, and hence, in the mainten-ance of the system's equilibrium; the under- or overfunction of human immune system may result in malaria and influence its severity; (3 coadaptation depends on genetic and epigenetic phenomena occurring at the interfaces of the components of the system, and may involve exchange of infectrons (genes or gene fragments between the partners; (4 plasmodia and mosquitoes have been submitted to selective pressures, leading to adaptation, for an extremely long while and are, therefore, endowed with the capacity to circumvent both natural (immunity and artificial (drugs, insecticides, vaccines measures aiming at destroying them; (5 since malaria represents disequilibrium of the system HPM, its control should aim at maintaining or restoring this equilibrium; (6 the disequilibrium of integrated systems involves the disequilibrium of their components, therefore the maintenance or restoration of the system's equilibrium depend on the adoption of integrated and coordinated measures acting on all components, that means

  10. Type I Interferon Transcriptional Signature in Neutrophils and Low-Density Granulocytes Are Associated with Tissue Damage in Malaria

    Directory of Open Access Journals (Sweden)

    Bruno Coelho Rocha

    2015-12-01

    Full Text Available Neutrophils are the most abundant leukocyte population in the bloodstream, the primary compartment of Plasmodium sp. infection. However, the role of these polymorphonuclear cells in mediating either the resistance or the pathogenesis of malaria is poorly understood. We report that circulating neutrophils from malaria patients are highly activated, as indicated by a strong type I interferon transcriptional signature, increased expression of surface activation markers, enhanced release of reactive oxygen species and myeloperoxidase, and a high frequency of low-density granulocytes. The activation of neutrophils was associated with increased levels of serum alanine and aspartate aminotransferases, indicating liver damage. In a rodent malaria model, we observed intense recruitment of neutrophils to liver sinusoids. Neutrophil migration and IL-1β and chemokine expression as well as liver damage were all dependent on type I interferon signaling. The data suggest that type I interferon signaling has a central role in neutrophil activation and malaria pathogenesis.

  11. Nanomedicine against malaria.

    Science.gov (United States)

    Urbán, Patricia; Fernàndez-Busquets, Xavier

    2014-01-01

    Malaria is arguably one of the main medical concerns worldwide because of the numbers of people affected, the severity of the disease and the complexity of the life cycle of its causative agent, the protist Plasmodium sp. The clinical, social and economic burden of malaria has led for the last 100 years to several waves of serious efforts to reach its control and eventual eradication, without success to this day. With the advent of nanoscience, renewed hopes have appeared of finally obtaining the long sought-after magic bullet against malaria in the form of a nanovector for the targeted delivery of antimalarial drugs exclusively to Plasmodium-infected cells. Different types of encapsulating structure, targeting molecule, and antimalarial compound will be discussed for the assembly of Trojan horse nanocapsules capable of targeting with complete specificity diseased cells and of delivering inside them their antimalarial cargo with the objective of eliminating the parasite with a single dose. Nanotechnology can also be applied to the discovery of new antimalarials through single-molecule manipulation approaches for the identification of novel drugs targeting essential molecular components of the parasite. Finally, methods for the diagnosis of malaria can benefit from nanotools applied to the design of microfluidic-based devices for the accurate identification of the parasite's strain, its precise infective load, and the relative content of the different stages of its life cycle, whose knowledge is essential for the administration of adequate therapies. The benefits and drawbacks of these nanosystems will be considered in different possible scenarios, including cost-related issues that might be hampering the development of nanotechnology-based medicines against malaria with the dubious argument that they are too expensive to be used in developing areas.

  12. Use of integrated malaria management reduces malaria in Kenya.

    Directory of Open Access Journals (Sweden)

    Bernard A Okech

    Full Text Available BACKGROUND: During an entomological survey in preparation for malaria control interventions in Mwea division, the number of malaria cases at the Kimbimbi sub-district hospital was in a steady decline. The underlying factors for this reduction were unknown and needed to be identified before any malaria intervention tools were deployed in the area. We therefore set out to investigate the potential factors that could have contributed to the decline of malaria cases in the hospital by analyzing the malaria control knowledge, attitudes and practices (KAP that the residents in Mwea applied in an integrated fashion, also known as integrated malaria management (IMM. METHODS: Integrated Malaria Management was assessed among community members of Mwea division, central Kenya using KAP survey. The KAP study evaluated community members' malaria disease management practices at the home and hospitals, personal protection measures used at the household level and malaria transmission prevention methods relating to vector control. Concurrently, we also passively examined the prevalence of malaria parasite infection via outpatient admission records at the major referral hospital in the area. In addition we studied the mosquito vector population dynamics, the malaria sporozoite infection status and entomological inoculation rates (EIR over an 8 month period in 6 villages to determine the risk of malaria transmission in the entire division. RESULTS: A total of 389 households in Mwea division were interviewed in the KAP study while 90 houses were surveyed in the entomological study. Ninety eight percent of the households knew about malaria disease while approximately 70% of households knew its symptoms and methods to manage it. Ninety seven percent of the interviewed households went to a health center for malaria diagnosis and treatment. Similarly a higher proportion (81% used anti-malarial medicines bought from local pharmacies. Almost 90% of households reported

  13. Frequently Asked Questions (FAQs) about Malaria

    Science.gov (United States)

    ... disease maintains a vicious cycle of disease and poverty. Top of Page How People Get Malaria (Transmission) ... a list of all the places in the world where malaria transmission occurs and the malaria drugs ...

  14. Prevalence and Parasite Density of Asymptomatic Malaria ...

    African Journals Online (AJOL)

    Prevalence and Parasite Density of Asymptomatic Malaria Parasitemia among Unbooked .... of two experienced laboratory scientists dedicated to the study to ensure quality control. .... Roll Back Malaria Annual Report. Abuja: Malaria Control.

  15. Filariasis attenuates anemia and proinflammatory responses associated with clinical malaria: a matched prospective study in children and young adults.

    Science.gov (United States)

    Dolo, Housseini; Coulibaly, Yaya I; Dembele, Benoit; Konate, Siaka; Coulibaly, Siaka Y; Doumbia, Salif S; Diallo, Abdallah A; Soumaoro, Lamine; Coulibaly, Michel E; Diakite, Seidina A S; Guindo, Aldiouma; Fay, Michael P; Metenou, Simon; Nutman, Thomas B; Klion, Amy D

    2012-01-01

    Wuchereria bancrofti (Wb) and Mansonella perstans (Mp) are blood-borne filarial parasites that are endemic in many countries of Africa, including Mali. The geographic distribution of Wb and Mp overlaps considerably with that of malaria, and coinfection is common. Although chronic filarial infection has been shown to alter immune responses to malaria parasites, its effect on clinical and immunologic responses in acute malaria is unknown. To address this question, 31 filaria-positive (FIL+) and 31 filaria-negative (FIL-) children and young adults, matched for age, gender and hemoglobin type, were followed prospectively through a malaria transmission season. Filarial infection was defined by the presence of Wb or Mp microfilariae on calibrated thick smears performed between 10 pm and 2 am and/or by the presence of circulating filarial antigen in serum. Clinical malaria was defined as axillary temperature ≥37.5°C or another symptom or sign compatible with malaria infection plus the presence of asexual malaria parasites on a thick blood smear. Although the incidence of clinical malaria, time to first episode, clinical signs and symptoms, and malaria parasitemia were comparable between the two groups, geometric mean hemoglobin levels were significantly decreased in FIL- subjects at the height of the transmission season compared to FIL+ subjects (11.4 g/dL vs. 12.5 g/dL, p<0.01). Plasma levels of IL-1ra, IP-10 and IL-8 were significantly decreased in FIL+ subjects at the time of presentation with clinical malaria (99, 2145 and 49 pg/ml, respectively as compared to 474, 5522 and 247 pg/ml in FIL- subjects). These data suggest that pre-existent filarial infection attenuates immune responses associated with severe malaria and protects against anemia, but has little effect on susceptibility to or severity of acute malaria infection. The apparent protective effect of filarial infection against anemia is intriguing and warrants further study in a larger cohort.

  16. Can plant biotechnology help break the HIV-malaria link?

    Science.gov (United States)

    Vamvaka, E; Twyman, R M; Christou, P; Capell, T

    2014-01-01

    The population of sub-Saharan Africa is at risk from multiple, poverty-related endemic diseases. HIV and malaria are the most prevalent, but they disproportionately affect different groups of people, i.e. HIV predominantly affects sexually-active adults whereas malaria has a greater impact on children and pregnant women. Nevertheless, there is a significant geographical and epidemiological overlap which results in bidirectional and synergistic interactions with important consequences for public health. The immunosuppressive effects of HIV increase the risk of infection when individuals are exposed to malaria parasites and also the severity of malaria symptoms. Similarly, acute malaria can induce a temporary increase in the HIV viral load. HIV is associated with a wide range of opportunistic infections that can be misdiagnosed as malaria, resulting in the wasteful misuse of antimalarial drugs and a failure to address the genuine cause of the disease. There is also a cumulative risk of toxicity when antiretroviral and antimalarial drugs are given to the same patients. Synergistic approaches involving the control of malaria as a strategy to fight HIV/AIDS and vice versa are therefore needed in co-endemic areas. Plant biotechnology has emerged as a promising approach to tackle poverty-related diseases because plant-derived drugs and vaccines can be produced inexpensively in developing countries and may be distributed using agricultural infrastructure without the need for a cold chain. Here we explore some of the potential contributions of plant biotechnology and its integration into broader multidisciplinary public health programs to combat the two diseases in developing countries. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Co-infection of Malaria and Crimean-Congo Hemorrhagic Fever

    Directory of Open Access Journals (Sweden)

    B Sharifi-Mood

    2011-09-01

    Full Text Available Southeast of Iran is an endemic area for Malaria and Crimean-Congo hemorrhagic fever (CCHF. In 1999, we faced with an outbreak of CCHF in Sistan and Baluchistan Province, in the border of Paki­stan and Afghanistan. The most cases of Malaria in Iran are also reported from this area. This arti­cle presents a 17-year- old woman who admitted to our hospital because of acute fever, head­ache, epistaxis, hemorrhagic lesions on the skin and vaginal bleeding. Finally, she was recog­nized as a case that was co -infected with CCHF and malaria.

  18. World Malaria Report: time to acknowledge Plasmodium knowlesi malaria.

    Science.gov (United States)

    Barber, Bridget E; Rajahram, Giri S; Grigg, Matthew J; William, Timothy; Anstey, Nicholas M

    2017-03-31

    The 2016 World Health Organization (WHO) World Malaria Report documents substantial progress towards control and elimination of malaria. However, major challenges remain. In some regions of Southeast Asia, the simian parasite Plasmodium knowlesi has emerged as an important cause of human malaria, and the authors believe this species warrants regular inclusion in the World Malaria Report. Plasmodium knowlesi is the most common cause of malaria in Malaysia, and cases have also been reported in nearly all countries of Southeast Asia. Outside of Malaysia, P. knowlesi is frequently misdiagnosed by microscopy as Plasmodium falciparum or Plasmodium vivax. Thus, P. knowlesi may be underdiagnosed in affected regions and its true incidence underestimated. Acknowledgement in the World Malaria Report of the regional importance of P. knowlesi will facilitate efforts to improve surveillance of this emerging parasite. Furthermore, increased recognition will likely lead to improved delivery of effective treatment for this potentially fatal infection, as has occurred in Malaysia where P. knowlesi case-fatality rates have fallen despite rising incidence. In a number of knowlesi-endemic countries, substantial progress has been made towards the elimination of P. vivax and P. falciparum. However, efforts to eliminate these human-only species should not preclude efforts to reduce human malaria from P. knowlesi. The regional importance of knowlesi malaria was recognized by the WHO with its recent Evidence Review Group meeting on knowlesi malaria to address strategies for prevention and mitigation. The WHO World Malaria Report has an appropriate focus on falciparum and vivax malaria, the major causes of global mortality and morbidity. However, the authors hope that in future years this important publication will also incorporate data on the progress and challenges in reducing knowlesi malaria in regions where transmission occurs.

  19. Rodent consumption in Khon Kaen Province, Thailand.

    Science.gov (United States)

    Suwannarong, Kanokwan; Chapman, Robert S

    2014-09-01

    Rodents are important reservoirs of rodent-borne infections worldwide, including Southeast Asia and Northeast Thailand (Isaan), where rodent consumption may be a source of rodent-borne diseases. The behavior of consuming rodents is related to a population's traditions, knowledge, cultural, and household contexts, among other factors. This cross-sectional survey was conducted in Khon Kaen Province, Thailand during November-December 2011. It aimed to elicit information about rodent consumption among residents of this province, and to identify factors associated with rodent consumption there. Multiple logistic regression analysis indicated that male gender, large family size, and use of rainwater as the main source of drinking water were positively associated with reported rodent consumption in this province, while having proper knowledge/attitudes towards animal-borne disease was negatively associated. These results provide evidence-base information for further studies, such as participatory ac- tion research, to further explore how people interact with rodents in different contexts. Further research is also needed to characterize risk of zoonotic diseases in relation to rodent consumption.

  20. Malaria-induced changes in host odors enhance mosquito attraction.

    Science.gov (United States)

    De Moraes, Consuelo M; Stanczyk, Nina M; Betz, Heike S; Pulido, Hannier; Sim, Derek G; Read, Andrew F; Mescher, Mark C

    2014-07-29

    Vector-borne pathogens may alter traits of their primary hosts in ways that influence the frequency and nature of interactions between hosts and vectors. Previous work has reported enhanced mosquito attraction to host organisms infected with malaria parasites but did not address the mechanisms underlying such effects. Here we document malaria-induced changes in the odor profiles of infected mice (relative to healthy individuals) over the course of infection, as well as effects on the attractiveness of infected hosts to mosquito vectors. We observed enhanced mosquito attraction to infected mice during a key period after the subsidence of acute malaria symptoms, but during which mice remained highly infectious. This attraction corresponded to an overall elevation in the volatile emissions of infected mice observed during this period. Furthermore, data analyses--using discriminant analysis of principal components and random forest approaches--revealed clear differences in the composition of the volatile blends of infected and healthy individuals. Experimental manipulation of individual compounds that exhibited altered emission levels during the period when differential vector attraction was observed also elicited enhanced mosquito attraction, indicating that compounds being influenced by malaria infection status also mediate vector host-seeking behavior. These findings provide important insights into the cues that mediate vector attraction to hosts infected with transmissible stages of malaria parasites, as well as documenting characteristic changes in the odors of infected individuals that may have potential value as diagnostic biomarkers of infection.

  1. [Current epidemiological malaria situation in Kyrgyzstan (1995-1999)].

    Science.gov (United States)

    Abdikarimov, S T

    2001-01-01

    experience with its control and who can define the highest priorities and the most appropriate and effective within the Global Malaria Control Strategy at the current stage. Laboratory services are in need of considerable support: stocks of essential supplies for laboratory tests are almost exhausted, there is a shortage of essential equipment, the staff is not well enough trained. There is an acute shortage of insecticides and larvicides for mosquito control. Entomologists have no sufficient insect control equipment to treat water areas (e.g. sprayers), there is no equipment for monitoring water areas or introducing larvicidal fishlaria (Gambusiae) either, and local monitoring is hampered by shortages of vehicles, fuel, and lubricants. Since malaria control is an urgent problem, Kyrgyzstan has developed a comprehensive and integrated malaria programme for 2000-2004 and a plan of actions to study malaria vector resistance to insecticides in the Republic of Kyrgyzstan in 2000.

  2. Rapid identification of genes controlling virulence and immunity in malaria parasites

    KAUST Repository

    Abkallo, Hussein M.

    2017-07-13

    Identifying the genetic determinants of phenotypes that impact disease severity is of fundamental importance for the design of new interventions against malaria. Here we present a rapid genome-wide approach capable of identifying multiple genetic drivers of medically relevant phenotypes within malaria parasites via a single experiment at single gene or allele resolution. In a proof of principle study, we found that a previously undescribed single nucleotide polymorphism in the binding domain of the erythrocyte binding like protein (EBL) conferred a dramatic change in red blood cell invasion in mutant rodent malaria parasites Plasmodium yoelii. In the same experiment, we implicated merozoite surface protein 1 (MSP1) and other polymorphic proteins, as the major targets of strain-specific immunity. Using allelic replacement, we provide functional validation of the substitution in the EBL gene controlling the growth rate in the blood stages of the parasites.

  3. Rapid identification of genes controlling virulence and immunity in malaria parasites

    Science.gov (United States)

    Xangsayarath, Phonepadith; Tang, Jianxia; Yahata, Kazuhide; Zoungrana, Augustin; Mitaka, Hayato; Acharjee, Arita; Datta, Partha P.; Hunt, Paul; Carter, Richard; Kaneko, Osamu; Mustonen, Ville; Pain, Arnab

    2017-01-01

    Identifying the genetic determinants of phenotypes that impact disease severity is of fundamental importance for the design of new interventions against malaria. Here we present a rapid genome-wide approach capable of identifying multiple genetic drivers of medically relevant phenotypes within malaria parasites via a single experiment at single gene or allele resolution. In a proof of principle study, we found that a previously undescribed single nucleotide polymorphism in the binding domain of the erythrocyte binding like protein (EBL) conferred a dramatic change in red blood cell invasion in mutant rodent malaria parasites Plasmodium yoelii. In the same experiment, we implicated merozoite surface protein 1 (MSP1) and other polymorphic proteins, as the major targets of strain-specific immunity. Using allelic replacement, we provide functional validation of the substitution in the EBL gene controlling the growth rate in the blood stages of the parasites. PMID:28704525

  4. Prediction of outcome in adults with severe falciparum malaria: a new scoring system

    Directory of Open Access Journals (Sweden)

    Mishra Rajalaxmi

    2007-02-01

    Full Text Available Abstract Background Mortality of falciparum malaria is related to the presence of severe complications. However, no scoring system is available to predict outcome of these patients. The aim of this paper was to devise a simple and reliable malaria prognosis score (MPS to predict the outcome of adults with severe malaria. Methods All slide-positive severe falciparum malaria patients admitted to Ispat General Hospital were studied. Eight clinical parameters that may potentially differentiate or influence the outcome were identified to predict recovery or death Results Of 248 severe malaria cases, 35 died. There were 212 adults (34 deaths and 36 children (one death. The malaria score for adults was (MSA = 1(severe anaemia + 2 (acute renal failure + 3(Respiratory distress +4 (cerebral malaria. The MSA ranges from 0 to 10. The mortality was 2% for MSA 0 – 2; 10% for MSA 3–4, 40% for MSA 5–6 and 90% for MSA 7 or more. The sensitivity is 89.9% and positive predictive value is 94.1% when 5 is taken as the cut off value. Conclusion MSA is a simple and sensitive predictor. It can be administered rapidly and repeatedly to prognosticate the outcome of severe malaria in adults. It can help the treating doctor to assess the patient as well as to communicate to the relatives of the patients about prognosis. The score needs revalidation in other geographical areas.

  5. Evaluation of a malaria antibody enzyme immunoassay for use in blood screening

    Directory of Open Access Journals (Sweden)

    Jun Seo Oh

    2008-02-01

    Full Text Available Transfusion-transmitted malaria is rare, but it may produce severe problem in the safety of blood transfusion due to the lack of reliable procedure to evaluate donors potentially exposed to malaria. Here, we evaluated a new enzyme-linked immunosorbent assay malaria antibody test (ELISA malaria antibody test, DiaMed, Switzerland to detect antibodies to Plasmodium vivax (the indigenous malaria in the blood samples in the Republic of Korea (ROK. Blood samples of four groups were obtained and analyzed; 100 samples from P.vivax infected patients, 35 from recovery patients, 366 from normal healthy individuals, and 325 from domestic travelers of non-endemic areas residents to risky areas of ROK. P.vivax antibody levels by ELISA were then compared to the results from microscopic examination and polymerase chain reaction (PCR test. As a result, the ELISA malaria antibody test had a clinical sensitivity of 53.0% and a clinical specificity of 94.0% for P.vivax. Twenty out of 325 domestic travelers (6.2% were reactive and 28 cases (8.6% were doubtful. Of the reactive and doubtful cases, only two were confirmed as acute malaria by both microscopy and PCR test. Thus we found that the ELISA malaria antibody test was insufficiently sensitive for blood screening of P.vivax in ROK.

  6. Auditing laboratory rodent biosecurity programs.

    Science.gov (United States)

    Porter, William P; Horn, Mandy J; Cooper, Dale M; Klein, Hilton J

    2013-10-22

    A rodent biosecurity program that includes periodic evaluation of procedures used in an institution's vivarium can be used to ensure that best practices are in place to prevent a microbial pathogen outbreak. As a result of an ongoing comprehensive biosecurity review within their North American and European production facilities, the authors developed a novel biosecurity auditing process and worksheet that could be useful in other animal care and use operations. The authors encourage other institutions to consider initiating similar audits of their biosecurity programs to protect the health of their laboratory animals.

  7. Malaria's deadly grip

    DEFF Research Database (Denmark)

    Smith, Joseph D; Rowe, J Alexandra; Higgins, Matthew K

    2013-01-01

    Cytoadhesion of Plasmodium falciparum-infected erythrocytes to host microvasculature is a key virulence determinant. Parasite binding is mediated by a large family of clonally variant adhesion proteins, termed P. falciparum erythrocyte membrane protein 1 (PfEMP1), encoded by var genes and expressed...... at the infected erythrocyte surface. Although PfEMP1 proteins have extensively diverged under opposing selection pressure to maintain ligand binding while avoiding antibody-mediated detection, recent work has revealed they can be classified into different groups based on chromosome location and domain composition......EMP1 subtypes appear to be specialized for infection of malaria naïve hosts. Here, we discuss recent findings on the origins and evolution of the var gene family, the structure-function of PfEMP1 proteins, and a distinct subset of PfEMP1 variants that have been associated with severe childhood malaria....

  8. Transfection of malaria parasites.

    Science.gov (United States)

    Waters, A P; Thomas, A W; van Dijk, M R; Janse, C J

    1997-10-01

    The stable genetic transformation of three phylogenetically diverse species of Plasmodium, the parasitic etiological agent of malaria, is now possible. The parasite is haploid throughout the vast majority of its life cycle. Therefore with the single selectable marker activity and protocols currently available, it is possible not only to express introduced transgenes but also to study the effects of site-specific homologous recombination such as gene knockout. Transgene expression will allow the detailed study of many aspects of the cellular biology of malaria parasites, for example, the mechanisms underlying drug resistance and protein trafficking. We describe here the methods for propagation of the two animal models (Plasmodium berghei and Plasmodium knowlesi) and for transfection of these two species and the human parasite, Plasmodium falciparum. Examples of transgene expression are given.

  9. PENELITIAN OBAT ANTI MALARIA

    Directory of Open Access Journals (Sweden)

    Emiliana Tjitra

    2012-09-01

    Full Text Available Some sensitivity tests of antimalarial drugs had been done by National Institute of Health Research and Development in collaboration with Directorate General of Communicable Disease Control and Environment Health, Naval Medical Research Unit No.2 and Faculty of Medicine University of Indonesia. In-vivo and or in-vitro Plasmodium falciparum multidrug resistance was reported from 11 provinces : Aceh, North Sumatera, Riau, Lampung, West Java, Jakarta (imported case, Central Java, East Kalimantan, South Sulawesi, East Nusa Tenggara and Irian Jaya. Only quinine had a good response for treatment of falciparum malaria resistant to multidrug. R falciparum resistant to mefloquine or halofantrine was found although it was not available in Indonesia yet. Chloroquine prophylaxis using standard dose was still effective in Tanjung Pinang and Central Java. To support the successfulness of treatment in malaria control programme, further studies on alternative antimalaria drugs is needed.

  10. Targeting Plasmodium PI(4)K to eliminate malaria

    Science.gov (United States)

    McNamara, Case W.; Lee, Marcus C. S.; Lim, Chek Shik; Lim, Siau Hoi; Roland, Jason; Nagle, Advait; Simon, Oliver; Yeung, Bryan K. S.; Chatterjee, Arnab K.; McCormack, Susan L.; Manary, Micah J.; Zeeman, Anne-Marie; Dechering, Koen J.; Kumar, T. R. Santha; Henrich, Philipp P.; Gagaring, Kerstin; Ibanez, Maureen; Kato, Nobutaka; Kuhen, Kelli L.; Fischli, Christoph; Rottmann, Matthias; Plouffe, David M.; Bursulaya, Badry; Meister, Stephan; Rameh, Lucia; Trappe, Joerg; Haasen, Dorothea; Timmerman, Martijn; Sauerwein, Robert W.; Suwanarusk, Rossarin; Russell, Bruce; Renia, Laurent; Nosten, Francois; Tully, David C.; Kocken, Clemens H. M.; Glynne, Richard J.; Bodenreider, Christophe; Fidock, David A.; Diagana, Thierry T.; Winzeler, Elizabeth A.

    2013-12-01

    Achieving the goal of malaria elimination will depend on targeting Plasmodium pathways essential across all life stages. Here we identify a lipid kinase, phosphatidylinositol-4-OH kinase (PI(4)K), as the target of imidazopyrazines, a new antimalarial compound class that inhibits the intracellular development of multiple Plasmodium species at each stage of infection in the vertebrate host. Imidazopyrazines demonstrate potent preventive, therapeutic, and transmission-blocking activity in rodent malaria models, are active against blood-stage field isolates of the major human pathogens P. falciparum and P. vivax, and inhibit liver-stage hypnozoites in the simian parasite P. cynomolgi. We show that imidazopyrazines exert their effect through inhibitory interaction with the ATP-binding pocket of PI(4)K, altering the intracellular distribution of phosphatidylinositol-4-phosphate. Collectively, our data define PI(4)K as a key Plasmodium vulnerability, opening up new avenues of target-based discovery to identify drugs with an ideal activity profile for the prevention, treatment and elimination of malaria.

  11. Targeting Plasmodium PI(4)K to eliminate malaria.

    Science.gov (United States)

    McNamara, Case W; Lee, Marcus C S; Lim, Chek Shik; Lim, Siau Hoi; Roland, Jason; Nagle, Advait; Simon, Oliver; Yeung, Bryan K S; Chatterjee, Arnab K; McCormack, Susan L; Manary, Micah J; Zeeman, Anne-Marie; Dechering, Koen J; Kumar, T R Santha; Henrich, Philipp P; Gagaring, Kerstin; Ibanez, Maureen; Kato, Nobutaka; Kuhen, Kelli L; Fischli, Christoph; Rottmann, Matthias; Plouffe, David M; Bursulaya, Badry; Meister, Stephan; Rameh, Lucia; Trappe, Joerg; Haasen, Dorothea; Timmerman, Martijn; Sauerwein, Robert W; Suwanarusk, Rossarin; Russell, Bruce; Renia, Laurent; Nosten, Francois; Tully, David C; Kocken, Clemens H M; Glynne, Richard J; Bodenreider, Christophe; Fidock, David A; Diagana, Thierry T; Winzeler, Elizabeth A

    2013-12-12

    Achieving the goal of malaria elimination will depend on targeting Plasmodium pathways essential across all life stages. Here we identify a lipid kinase, phosphatidylinositol-4-OH kinase (PI(4)K), as the target of imidazopyrazines, a new antimalarial compound class that inhibits the intracellular development of multiple Plasmodium species at each stage of infection in the vertebrate host. Imidazopyrazines demonstrate potent preventive, therapeutic, and transmission-blocking activity in rodent malaria models, are active against blood-stage field isolates of the major human pathogens P. falciparum and P. vivax, and inhibit liver-stage hypnozoites in the simian parasite P. cynomolgi. We show that imidazopyrazines exert their effect through inhibitory interaction with the ATP-binding pocket of PI(4)K, altering the intracellular distribution of phosphatidylinositol-4-phosphate. Collectively, our data define PI(4)K as a key Plasmodium vulnerability, opening up new avenues of target-based discovery to identify drugs with an ideal activity profile for the prevention, treatment and elimination of malaria.

  12. Pathogenesis of malaria revisited.

    Science.gov (United States)

    Dasari, Prasad; Bhakdi, Sucharit

    2012-11-01

    Plasmodium falciparum malaria claims 1 million lives around the globe every year. Parasitemia can reach remarkably high levels. The developing parasite digests hemoglobin and converts the waste product to hemozoin alias malaria pigment. These processes occur in a vesicular compartment named the digestive vacuole (DV). Each parasitized cell releases one DV upon rupture. Myriads of DVs thus gain entry into the blood, but whether they trigger pathobiological events has never been investigated. We recently discovered that the DV membrane simultaneously activates the two major enzyme cascades in blood, complement and coagulation. Activation of both is known to occur in patients with severe malaria, so discovery of the common trigger has large consequences. The DV membrane but not the merozoite has the capacity to spontaneously activate the alternative complement and intrinsic clotting pathway. Ejection of merozoites and the DV into the bloodstream, therefore, results in selective opsonization and phagocytosis of the DV, leaving merozoites free to invade new cells. The DV membrane furthermore has the capacity to assemble prothrombinase, the key convertase of the intrinsic clotting pathway. The dual capacity of the DV to activate both complement and coagulation can be suppressed by low-molecular-weight dextran sulfate. This agent protects experimental animals from the detrimental consequences, resulting from intravenous application of purified DVs. Phagocytosis of DVs not only deploys PMN away from merozoites, but also drives the cells into a state of functional exhaustion. This may be one reason for the enhanced susceptibility of patients with severe malaria toward systemic bacterial infections. Together, these findings indicate that the DV may represent a hitherto unrecognized, important determinant of parasite pathogenicity.

  13. Acute respiratory distress syndrome and acute renal failure from Plasmodium ovale infection with fatal outcome.

    Science.gov (United States)

    Lau, Yee-Ling; Lee, Wenn-Chyau; Tan, Lian-Huat; Kamarulzaman, Adeeba; Syed Omar, Sharifah Faridah; Fong, Mun-Yik; Cheong, Fei-Wen; Mahmud, Rohela

    2013-11-04

    Plasmodium ovale is one of the causative agents of human malaria. Plasmodium ovale infection has long been thought to be non-fatal. Due to its lower morbidity, P. ovale receives little attention in malaria research. Two Malaysians went to Nigeria for two weeks. After returning to Malaysia, they fell sick and were admitted to different hospitals. Plasmodium ovale parasites were identified from blood smears of these patients. The species identification was further confirmed with nested PCR. One of them was successfully treated with no incident of relapse within 12-month medical follow-up. The other patient came down with malaria-induced respiratory complication during the course of treatment. Although parasites were cleared off the circulation, the patient's condition worsened. He succumbed to multiple complications including acute respiratory distress syndrome and acute renal failure. Sequencing of the malaria parasite DNA from both cases, followed by multiple sequence alignment and phylogenetic tree construction suggested that the causative agent for both malaria cases was P. ovale curtisi. In this report, the differences between both cases were discussed, and the potential capability of P. ovale in causing severe complications and death as seen in this case report was highlighted. Plasmodium ovale is potentially capable of causing severe complications, if not death. Complete travel and clinical history of malaria patient are vital for successful diagnoses and treatment. Monitoring of respiratory and renal function of malaria patients, regardless of the species of malaria parasites involved is crucial during the course of hospital admission.

  14. Malaria Diagnostics Market grows with increasing public awareness on malaria

    OpenAIRE

    Smita Deshmukh

    2016-01-01

    Transparency Market Research Reports incorporated a definite business overview and investigation inclines on "Malaria Diagnostics Market". This report likewise incorporates more illumination about fundamental review of the business including definitions, requisitions and worldwide business sector industry structure.   Read Full Report: http://www.transparencymarketresearch.com/malaria-diagnostics-market.html

  15. Sleep deprivation and anxiety in humans and rodents--translational considerations and hypotheses.

    Science.gov (United States)

    Pires, Gabriel Natan; Tufik, Sergio; Andersen, Monica Levy

    2015-10-01

    The effects of acute sleep deprivation on anxiety are the focus of controversy in the literature. While clinical research studies on the effects of sleep deprivation seem to show a consistent increase in acute anxiety, rodent studies have produced inconsistent results, with some experiments pointing to anxiogenesis and others to anxiolysis. Such observations impair the translational applicability of rodent models on the paradigm between sleep deprivation and anxiety. Current studies fail in the very basic principle of biomedical translational research: to provide relevant and reliable knowledge from basic experimental science that can be applied in clinical environments. Possible explanations for the disparity between human and animal studies include the accuracy of both human and rodent research, the ability of current behavioral protocols to truly reflect the anxiety response of rodents to sleep deprivation, and the nature of sleep deprivation-induced anxiety in rodents. Based on these hypotheses, we performed a brief overview of the literature on the relationship between sleep deprivation and anxiety and propose a research agenda that could lead to a better understanding of the reasons for the discrepancies found in the literature and provide more reliable data on the translational relationship between sleep deprivation and anxiety.

  16. Urban resident attitudes toward rodents, rodent control products, and environmental effects

    Science.gov (United States)

    Rodent control in urban areas can result in the inadvertent mortality of non-target species (e.g., bobcats). However, there is little detailed information about rodent control practices of urban residents. Our objective was to evaluate urban rodent control behaviors in two area...

  17. Urban resident attitudes toward rodents, rodent control products, and environmental effects

    Science.gov (United States)

    Rodent control in urban areas can result in the inadvertent mortality of non-target species (e.g., bobcats). However, there is little detailed information about rodent control practices of urban residents. Our objective was to evaluate urban rodent control behaviors in two area...

  18. Urinary tubular protein-based biomarkers in the rodent model of cisplatin nephrotoxicity: a comparative analysis of serum creatinine, renal histology, and urinary KIM-1, NGAL, and NAG in the initiation, maintenance, and recovery phases of acute kidney injury.

    Science.gov (United States)

    Sinha, Vikash; Vence, Luis M; Salahudeen, Abdulla K

    2013-03-01

    Several biomarkers are becoming available for the early detection of acute kidney injury (AKI), but few have been directly compared. To compare urinary kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and N-acetyl glucosaminidase (NAG) against serum creatinine and renal histological score in the initiation, maintenance, and recovery phases of cisplatin (CP)-induced AKI. Sprague-Dawley rats (300-350 g) were injected once through their tail veins with CP (CP group) at 5.5 mg/kg or with same volume of normal saline vehicle (Control group). Rats were euthanized at 2, 4, 6, 12, and 24 hours, and on days 2, 3, 6, and 10 (n = 12 in the CP group and n = 6 in the Control group at each time point), and urine, blood, and kidney samples were analyzed. A significant increase in serum creatinine was noted by day 3 in the CP group versus Control group [1.46 (0.12) vs 0.28 (0.03) mg/dL; mean (SE); P CP group. Urinary kidney injury molecule-1 levels were significantly higher at 24 hours in the CP group than in the Control group [48.26 (13.13) vs 8.21 (3.31) pg/mg creatinine; P CP than in the Control group [NAG, 8.19 (0.82) vs 3.48 (0.40) pg/mg creatinine, P G 0.05; NGAL, 2911.80 (368.10) vs 1412.60 (250.20) pg/mg creatinine, P CP to discern the time course and pattern of expression.

  19. The utility of the small rodent electrocardiogram in toxicology.

    Science.gov (United States)

    Farraj, Aimen K; Hazari, Mehdi S; Cascio, Wayne E

    2011-05-01

    Extensive research has lead to a growing appreciation that the heart is acutely sensitive to a broad array of toxicants via multiple routes of exposure. These agents are as diverse as the antineoplastic drug doxorubicin and environmental agents including ambient air pollution. Adverse effects in the heart often manifest as a change in the electrocardiogram (ECG). The ECG has long been used in the clinic to assess human cardiovascular health. Surface electrocardiographic recordings (i.e., those made from the skin) in humans often help to detect abnormal myocardial impulse formation, conduction, cardiac rhythm disturbances, and altered autonomic regulation of the heart. In toxicology, the ECG provides a collection of end points that may be used to assess both the quality and magnitude of cardiac toxicity. Increasingly over the last two decades, the cardiotoxicity of agents have been characterized using small rodent electrocardiography. Additionally, tremendous insight into possible mechanisms of action of known human cardiotoxicants has been gained. Rat and mouse models offer a number of advantages relative to larger animals including lower cost, less variability, the availability of transgenic models, and a plethora of research tools. Modern day advances in small rodent electrocardiography have enabled assessments in conscious unrestrained animals and improved ECG interpretation. Thus, the incorporation of small rodent electrocardiographic assessments into toxicology studies may facilitate the screening of cardiotoxic potential and the elucidation of mechanisms of action. This review will discuss the utility of the small rodent ECG, various methodologies used to derive ECG data in rats and mice, and various applications in toxicology.

  20. Immunity to malaria in an era of declining malaria transmission.

    Science.gov (United States)

    Fowkes, Freya J I; Boeuf, Philippe; Beeson, James G

    2016-02-01

    With increasing malaria control and goals of malaria elimination, many endemic areas are transitioning from high-to-low-to-no malaria transmission. Reductions in transmission will impact on the development of naturally acquired immunity to malaria, which develops after repeated exposure to Plasmodium spp. However, it is currently unclear how declining transmission and malaria exposure will affect the development and maintenance of naturally acquired immunity. Here we review the key processes which underpin this knowledge; the amount of Plasmodium spp. exposure required to generate effective immune responses, the longevity of antibody responses and the ability to mount an effective response upon re-exposure through memory responses. Lastly we identify research priorities which will increase our understanding of how changing transmission will impact on malarial immunity.

  1. Newer approaches to malaria control.

    Science.gov (United States)

    Damodaran, Se; Pradhan, Prita; Pradhan, Suresh Chandra

    2011-07-01

    Malaria is the third leading cause of death due to infectious diseases affecting around 243 million people, causing 863,000 deaths each year, and is a major public health problem. Most of the malarial deaths occur in children below 5 years and is a major contributor of under-five mortality. As a result of environmental and climatic changes, there is a change in vector population and distribution, leading to resurgence of malaria at numerous foci. Resistance to antimalarials is a major challenge to malaria control and there are new drug developments, new approaches to treatment strategies, combination therapy to overcome resistance and progress in vaccine development. Now, artemisinin-based combination therapy is the first-line therapy as the malarial parasite has developed resistance to other antimalarials. Reports of artemisinin resistance are appearing and identification of new drug targets gains utmost importance. As there is a shift from malaria control to malaria eradication, more research is focused on malaria vaccine development. A malaria vaccine, RTS,S, is in phase III of development and may become the first successful one. Due to resistance to insecticides and lack of environmental sanitation, the conventional methods of vector control are turning out to be futile. To overcome this, novel strategies like sterile insect technique and transgenic mosquitoes are pursued for effective vector control. As a result of the global organizations stepping up their efforts with continued research, eradication of malaria can turn out to be a reality.

  2. Malaria vaccine: a current perspective

    Directory of Open Access Journals (Sweden)

    Shobhona Sharma

    2008-02-01

    Full Text Available The observation that inactivated Plasmodium sporozoites could protect against malaria is about a hundred years old. However, systematic demonstration of protection using irradiated sporozoites occurred in the nineteen-sixties, providing the impetus for the development of a malaria vaccine. In 1983, the circumsporozoite protein (CSP, a major sporozoite surface antigen, became the first Plasmodium gene to be cloned, and a CSP-based vaccine appeared imminent. Today, 25 years later, we are still without an effective malaria vaccine, despite considerable information regarding the genomics and proteomics of the malaria parasites. Although clinical immunity to malaria has been well-documented in adults living in malaria endemic areas, our understanding of the host-immune responses operating in such malaria immune persons remains poor, and limits the development of immune control of the disease. Currently, several antigen and adjuvant combinations have entered clinical trials, in which efficacy against experimental sporozoite challenge and/or exposure to natural infection is evaluated. This review collates information on the recent status of the field. Unresolved challenges facing the development of a malaria vaccine are also discussed.

  3. Malaria during pregnancy in Rwanda

    NARCIS (Netherlands)

    Rulisa, S.

    2014-01-01

    It appears that malaria in Rwanda is not a major contributor to adverse outcomes of pregnancy anymore from a public health perspective but it can still give problems in individual patients, also in areas of low malaria transmission. This thesis shows that for individual cases the current treatment o

  4. Malaria: toxins, cytokines and disease

    DEFF Research Database (Denmark)

    Jakobsen, P H; Bate, C A; Taverne, J;

    1995-01-01

    In this review the old concept of severe malaria as a toxic disease is re-examined in the light of recent discoveries in the field of cytokines. Animal studies suggest that the induction of TNF by parasite-derived molecules may be partly responsible for cerebral malaria and anemia, while hypoglyc...

  5. Reversible Audiometric Threshold Changes in Children with Uncomplicated Malaria

    Directory of Open Access Journals (Sweden)

    George O. Adjei

    2013-01-01

    Full Text Available Background. Plasmodium falciparum malaria, as well as certain antimalarial drugs, is associated with hearing impairment in adults. There is little information, however, on the extent, if any, of this effect in children, and the evidence linking artemisinin combination therapies (ACTs with hearing is inconclusive. Methods. Audiometry was conducted in children with uncomplicated malaria treated with artesunate-amodiaquine (n=37, artemether-lumefantrine (n=35, or amodiaquine (n=8 in Accra, Ghana. Audiometry was repeated 3, 7, and 28 days later and after 9 months. Audiometric thresholds were compared with those of a control group of children (n=57 from the same area. Findings. During the acute stage, hearing threshold levels of treated children were significantly elevated compared with controls (P<0.001. The threshold elevations persisted up to 28 days, but no differences in hearing thresholds were evident between treated children and controls after 9 months. The hearing thresholds of children treated with the two ACT regimens were comparable but lower than those of amodiaquine-treated children during acute illness. Interpretation. Malaria is the likely cause of the elevated hearing threshold levels during the acute illness, a finding that has implications for learning and development in areas of intense transmission, as well as for evaluating potential ototoxicity of new antimalarial drugs.

  6. Fats & Fakes : Towards improved control of malaria

    NARCIS (Netherlands)

    Visser, B.J.

    2017-01-01

    Effective malaria control reduced the malaria burden worldwide tremendously. Simultaneously, the epidemiology of malaria is changing and has become more complex. To continue the progress of the last decade, this thesis addressed several areas of importance in the field of malaria. Since effective ma

  7. Fats & Fakes : Towards improved control of malaria

    NARCIS (Netherlands)

    Visser, B.J.

    2017-01-01

    Effective malaria control reduced the malaria burden worldwide tremendously. Simultaneously, the epidemiology of malaria is changing and has become more complex. To continue the progress of the last decade, this thesis addressed several areas of importance in the field of malaria. Since effective

  8. Fats & Fakes : Towards improved control of malaria

    NARCIS (Netherlands)

    Visser, B.J.

    2017-01-01

    Effective malaria control reduced the malaria burden worldwide tremendously. Simultaneously, the epidemiology of malaria is changing and has become more complex. To continue the progress of the last decade, this thesis addressed several areas of importance in the field of malaria. Since effective ma

  9. Besnoitiosis in rodents from Colorado. [Parasitic infestations

    Energy Technology Data Exchange (ETDEWEB)

    Dagle, G E; Winsor, T F; Adee, R R

    1976-01-01

    Parasitic cysts of Besnoitia jellisoni (coccidia) were found in rodents (Peromyscus maniculatus and Spermophilus tridecemlineatus) trapped in Eastern Colorado. The parasite was associated with a granulomatous inflammatory reaction in the lungs of each rodent and was disseminated in several organs from one Peromyscus. The ultrastructural appearance of the merozoites and the cyst wall formed by the host cell were studied.

  10. Rodent Models for Metabolic Syndrome Research

    Directory of Open Access Journals (Sweden)

    Sunil K. Panchal

    2011-01-01

    Full Text Available Rodents are widely used to mimic human diseases to improve understanding of the causes and progression of disease symptoms and to test potential therapeutic interventions. Chronic diseases such as obesity, diabetes and hypertension, together known as the metabolic syndrome, are causing increasing morbidity and mortality. To control these diseases, research in rodent models that closely mimic the changes in humans is essential. This review will examine the adequacy of the many rodent models of metabolic syndrome to mimic the causes and progression of the disease in humans. The primary criterion will be whether a rodent model initiates all of the signs, especially obesity, diabetes, hypertension and dysfunction of the heart, blood vessels, liver and kidney, primarily by diet since these are the diet-induced signs in humans with metabolic syndrome. We conclude that the model that comes closest to fulfilling this criterion is the high carbohydrate, high fat-fed male rodent.

  11. Asymptomatic malaria, growth status, and anaemia among children in Lao People’s Democratic Republic: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Takeshi Akiyama

    2016-10-01

    Full Text Available Abstract Background Asymptomatic malaria can be observed in both stable endemic areas and unstable transmission areas. However, although much attention has been given to acute malaria infections, relatively little attention has been paid to asymptomatic malaria. Nonetheless, because the asymptomatic host serves as a reservoir for the malaria parasite, asymptomatic malaria is now recognized as an important obstacle to malaria elimination. Asymptomatic malaria is also associated with anaemia, a global public health problem with serious consequences on human health as well as social and economic development. In Lao People’s Democratic Republic (Lao PDR, malaria, anaemia, and malnutrition are serious public health concerns. However, few studies have focused on the relationship between these variables. Therefore, this study investigated the relationship between asymptomatic malaria, growth status, and the prevalence of anaemia among children aged 120 months old or younger in rural villages in Lao PDR. Methods In December 2010 and March 2011, data were collected from five villages in Savannakhet province. Anthropometric measurements, blood samples, and malaria rapid diagnostic tests were conducted. The presence of malaria was confirmed with polymerase chain reaction assays for Plasmodium falciparum. Underweight status, stunting, and anaemia were defined according to World Health Organization standards. Results The mean age of participants (n = 319 was 88.3 months old (Standard Deviation: 20.6, ranged from 30–119 months old, and 20 participants (6.3 % had an asymptomatic malaria infection, 92 (28.8 % were anaemic, 123 (38.6 % were underweight, and 137 (42.9 % were stunted. Stunted children were more likely to be infected with asymptomatic malaria [odds ratio (OR 3.34, 95 % confidence interval (CI 1.25–8.93], and asymptomatic malaria was associated with anaemia [OR 5.17, 95 % CI 1.99–13.43]. Conclusions These results suggest a

  12. Asymptomatic malaria, growth status, and anaemia among children in Lao People's Democratic Republic: a cross-sectional study.

    Science.gov (United States)

    Akiyama, Takeshi; Pongvongsa, Tiengkham; Phrommala, Souraxay; Taniguchi, Tomoyo; Inamine, Yuba; Takeuchi, Rie; Watanabe, Tadashi; Nishimoto, Futoshi; Moji, Kazuhiko; Kano, Shigeyuki; Watanabe, Hisami; Kobayashi, Jun

    2016-10-18

    Asymptomatic malaria can be observed in both stable endemic areas and unstable transmission areas. However, although much attention has been given to acute malaria infections, relatively little attention has been paid to asymptomatic malaria. Nonetheless, because the asymptomatic host serves as a reservoir for the malaria parasite, asymptomatic malaria is now recognized as an important obstacle to malaria elimination. Asymptomatic malaria is also associated with anaemia, a global public health problem with serious consequences on human health as well as social and economic development. In Lao People's Democratic Republic (Lao PDR), malaria, anaemia, and malnutrition are serious public health concerns. However, few studies have focused on the relationship between these variables. Therefore, this study investigated the relationship between asymptomatic malaria, growth status, and the prevalence of anaemia among children aged 120 months old or younger in rural villages in Lao PDR. In December 2010 and March 2011, data were collected from five villages in Savannakhet province. Anthropometric measurements, blood samples, and malaria rapid diagnostic tests were conducted. The presence of malaria was confirmed with polymerase chain reaction assays for Plasmodium falciparum. Underweight status, stunting, and anaemia were defined according to World Health Organization standards. The mean age of participants (n = 319) was 88.3 months old (Standard Deviation: 20.6, ranged from 30-119 months old), and 20 participants (6.3 %) had an asymptomatic malaria infection, 92 (28.8 %) were anaemic, 123 (38.6 %) were underweight, and 137 (42.9 %) were stunted. Stunted children were more likely to be infected with asymptomatic malaria [odds ratio (OR) 3.34, 95 % confidence interval (CI) 1.25-8.93], and asymptomatic malaria was associated with anaemia [OR 5.17, 95 % CI 1.99-13.43]. These results suggest a significant association between asymptomatic malaria and anaemia in

  13. The importance of human FcgammaRI in mediating protection to malaria.

    Directory of Open Access Journals (Sweden)

    Richard S McIntosh

    2007-05-01

    Full Text Available The success of passive immunization suggests that antibody-based therapies will be effective at controlling malaria. We describe the development of fully human antibodies specific for Plasmodium falciparum by antibody repertoire cloning from phage display libraries generated from immune Gambian adults. Although these novel reagents bind with strong affinity to malaria parasites, it remains unclear if in vitro assays are predictive of functional immunity in humans, due to the lack of suitable animal models permissive for P. falciparum. A potentially useful solution described herein allows the antimalarial efficacy of human antibodies to be determined using rodent malaria parasites transgenic for P. falciparum antigens in mice also transgenic for human Fc-receptors. These human IgG1s cured animals of an otherwise lethal malaria infection, and protection was crucially dependent on human FcgammaRI. This important finding documents the capacity of FcgammaRI to mediate potent antimalaria immunity and supports the development of FcgammaRI-directed therapy for human malaria.

  14. Trimethoprim-Sulfamethoxazole Prophylaxis During Live Malaria Sporozoite Immunization Induces Long-Lived, Homologous, and Heterologous Protective Immunity Against Sporozoite Challenge.

    Science.gov (United States)

    Hobbs, Charlotte V; Anderson, Charles; Neal, Jillian; Sahu, Tejram; Conteh, Solomon; Voza, Tatiana; Langhorne, Jean; Borkowsky, William; Duffy, Patrick E

    2017-01-01

    Trimethoprim-sulfamethoxazole (TMP-SMX) is widely used in malaria-endemic areas in human immunodeficiency virus (HIV)-infected children and HIV-uninfected, HIV-exposed children as opportunistic infection prophylaxis. Despite the known effects that TMP-SMX has in reducing clinical malaria, its impact on development of malaria-specific immunity in these children remains poorly understood. Using rodent malaria models, we previously showed that TMP-SMX, at prophylactic doses, can arrest liver stage development of malaria parasites and speculated that TMP-SMX prophylaxis during repeated malaria exposures would induce protective long-lived sterile immunity targeting pre-erythrocytic stage parasites in mice. Using the same models, we now demonstrate that repeated exposures to malaria parasites during TMP-SMX administration induces stage-specific and long-lived pre-erythrocytic protective anti-malarial immunity, mediated primarily by CD8(+) T-cells. Given the HIV infection and malaria coepidemic in sub-Saharan Africa, clinical studies aimed at determining the optimum duration of TMP-SMX prophylaxis in HIV-infected or HIV-exposed children must account for the potential anti-infection immunity effect of TMP-SMX prophylaxis. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  15. Malaria in Mauritania: retrospective and prospective overview.

    Science.gov (United States)

    Lekweiry, Khadijetou Mint; Salem, Mohamed Salem Ould Ahmedou; Basco, Leonardo K; Briolant, Sébastien; Hafid, Jamaleddine; Boukhary, Ali Ould Mohamed Salem

    2015-03-04

    Malaria has become a major public health problem in Mauritania since the 1990s, with an average of 181,000 cases per year and 2,233,066 persons at risk during 1995-2012. This paper provides the first publicly available overview of malaria incidence and distribution in Mauritania. Information on the burden and malaria species distribution is critical for guiding national efforts in malaria control. As the incidence of malaria changes over time, regular updates of epidemiological data are necessary.

  16. A Research Agenda for Malaria Eradication: Vaccines

    OpenAIRE

    ,

    2011-01-01

    Vaccines could be a crucial component of efforts to eradicate malaria. Current attempts to develop malaria vaccines are primarily focused on Plasmodium falciparum and are directed towards reducing morbidity and mortality. Continued support for these efforts is essential, but if malaria vaccines are to be used as part of a repertoire of tools for elimination or eradication of malaria, they will need to have an impact on malaria transmission. We introduce the concept of “vaccines that interrupt...

  17. CLINICAL ASPECTS OF UNCOMPLICATED AND SEVERE MALARIA

    OpenAIRE

    Alessandro Bartoloni; Lorenzo Zammarchi

    2012-01-01

    The first symptoms of malaria, common to all the different malaria species, are nonspecific and mimic a flu-like syndrome. Although fever represents the cardinal feature, clinical findings in malaria are extremely diverse and may range in severity from mild headache to serious complications leading to death, particularly in falciparum malaria. As the progression to these complications can be rapid, any malaria patient must be assessed and treated rapidly, and frequent observations are needed ...

  18. Clinical aspects of uncomplicated and severe malaria

    OpenAIRE

    Bartoloni A; Zammarchi L.

    2012-01-01

    The first symptoms of malaria, common to all the different malaria species, are nonspecific and mimic a flu-like syndrome. Although fever represents the cardinal feature, clinical findings in malaria are extremely diverse and may range in severity from mild headache to serious complications leading to death, particularly in falciparum malaria. As the progression to these complications can be rapid, any malaria patient must be assessed and treated rapidly, and frequent observations are needed ...

  19. Clinical Aspects of Uncomplicated and Severe Malaria

    OpenAIRE

    Bartoloni, Alessandro; Zammarchi, Lorenzo

    2012-01-01

    The first symptoms of malaria, common to all the different malaria species, are nonspecific and mimic a flu-like syndrome. Although fever represents the cardinal feature, clinical findings in malaria are extremely diverse and may range in severity from mild headache to serious complications leading to death, particularly in falciparum malaria. As the progression to these complications can be rapid, any malaria patient must be assessed and treated rapidly, and frequent observations are needed ...

  20. Influenza and malaria coinfection among young children in western Kenya, 2009-2011.

    Science.gov (United States)

    Thompson, Mark G; Breiman, Robert F; Hamel, Mary J; Desai, Meghna; Emukule, Gideon; Khagayi, Sammy; Shay, David K; Morales, Kathleen; Kariuki, Simon; Bigogo, Godfrey M; Njenga, M Kariuki; Burton, Deron C; Odhiambo, Frank; Feikin, Daniel R; Laserson, Kayla F; Katz, Mark A

    2012-12-01

    Although children malaria and influenza, little is known about coinfection. This retrospective, cross-sectional study in rural western Kenya examined outpatient visits and hospitalizations associated with febrile acute respiratory illness (ARI) during a 2-year period (July 2009-June 2011) in children malaria, whereas only 6% (149/2408) of malaria-positive patients were coinfected with influenza. Depending on age, coinfection was present in 4%-8% of outpatient visits and 1%-3% of inpatient admissions for febrile ARI. Children with influenza were less likely than those without to have malaria (risk ratio [RR], 0.57-0.76 across sites and ages), and children with malaria were less likely than those without to have influenza (RR, 0.36-0.63). Among coinfected children aged 24-59 months, hospital length of stay was 2.7 and 2.8 days longer than influenza-only-infected children at the 2 sites, and 1.3 and 3.1 days longer than those with malaria only (all P malaria and influenza was uncommon but associated with longer hospitalization than single infections among children 24-59 months of age.

  1. A decade of malaria during pregnancy in Brazil: what has been done concerning prevention and management

    Directory of Open Access Journals (Sweden)

    Paola Marchesini

    2014-08-01

    Full Text Available In Brazil, malaria remains a disease of major epidemiological importance because of the high number of cases in the Amazonian Region. Plasmodium spp infections during pregnancy are a significant public health problem with substantial risks for the pregnant woman, the foetus and the newborn child. In Brazil, the control of malaria during pregnancy is primarily achieved by prompt and effective treatment of the acute episodes. Thus, to assure rapid diagnosis and treatment for pregnant women with malaria, one of the recommended strategy for low transmission areas by World Health Organization and as part of a strategy by the Ministry of Health, the National Malaria Control Program has focused on integrative measures with woman and reproductive health. Here, we discuss the approach for the prevention and management of malaria during pregnancy in Brazil over the last 10 years (2003-2012 using morbidity data from Malaria Health Information System. Improving the efficiency and quality of healthcare and education and the consolidation of prevention programmes will be challenges in the control of malaria during pregnancy in the next decade.

  2. A decade of malaria during pregnancy in Brazil: what has been done concerning prevention and management.

    Science.gov (United States)

    Marchesini, Paola; Costa, Fabio Trindade Maranhão; Marinho, Claudio Romero Farias

    2014-08-01

    In Brazil, malaria remains a disease of major epidemiological importance because of the high number of cases in the Amazonian Region. Plasmodium spp infections during pregnancy are a significant public health problem with substantial risks for the pregnant woman, the foetus and the newborn child. In Brazil, the control of malaria during pregnancy is primarily achieved by prompt and effective treatment of the acute episodes. Thus, to assure rapid diagnosis and treatment for pregnant women with malaria, one of the recommended strategy for low transmission areas by World Health Organization and as part of a strategy by the Ministry of Health, the National Malaria Control Program has focused on integrative measures with woman and reproductive health. Here, we discuss the approach for the prevention and management of malaria during pregnancy in Brazil over the last 10 years (2003-2012) using morbidity data from Malaria Health Information System. Improving the efficiency and quality of healthcare and education and the consolidation of prevention programmes will be challenges in the control of malaria during pregnancy in the next decade.

  3. Towards early in vivo photoacoustic malaria diagnosis with 10,000-fold sensitivity improvement (Conference Presentation)

    Science.gov (United States)

    Carey, Kai A.; Menyaev, Yulian A.; Nedosekin, Dmitry A.; Sarimollaoglu, Mustafa; Galanzha, Ekaterina I.; Stumhofer, Jason S.; Zharov, Vladimir P.

    2017-03-01

    Roughly 0.6 million people die each year from malaria due to lack of early diagnosis and well-timed treatment. Our previous study demonstrated great potential of in vivo photoacoustic (PA) flow cytometry (PAFC) for early diagnosis of deadly diseases with focus on cancer and thromboembolic complications. Here we demonstrate potential of advanced PAFC platforms using new laser, ultrasound transducer array and recording system to detect infected red blood cells (iRBCs) with malaria-associated pigment hemozoin which has a higher PA contrast than blood background. Mature parasites of human infecting species such as P. falciparum characteristically sequester mature iRBCs in the capillary bed and display synchrony in their reproductive cycle. To address this issue prior to clinical application, new PAFC platform was verified in a pre-clinical study using new animal models. Specifically, we used P. chabaudi (a rodent malaria species that mimics the characteristics of the most virulent human counterpart) to estimate the detection sensitivity with immature ring-stage parasites in peripheral blood, compared PA signals from the differing species, and examined the relationship between PA signal amplitudes and level of blood oxygenation. Based on previous successful trials on melanoma patients with melanin as an intrinsic PA marker, which has similar absorption as hemozoin, we believe that after additional malaria-related clinical trials, PAFC with a small 1064 nm laser and wearable a cost-effective, easy-to-use, watch-like, safe PA probe will provide malaria diagnosis in humans at parasitemia levels 10e4 -times lower than the current gold standard of diagnosis, the Giemsa-stained blood smear. It can reduce malaria-related mortality by well-timed treatment, especially in children in malaria-endemic countries.

  4. Severe imported malaria in an intensive care unit: a review of 59 cases

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    Santos Lurdes C

    2012-03-01

    Full Text Available Abstract Background In view of the close relationship of Portugal with African countries, particularly former Portuguese colonies, the diagnosis of malaria is not a rare thing. When a traveller returns ill from endemic areas, malaria should be the number one suspect. World Health Organization treatment guidelines recommend that adults with severe malaria should be admitted to an intensive care unit (ICU. Methods Severe cases of malaria in patients admitted to an ICU were reviewed retrospectively (1990-2011 and identification of variables associated with in-ICU mortality performed. Malaria prediction score (MPS, malaria score for adults (MSA, simplified acute physiology score (SAPSII and a score based on WHO's malaria severe criteria were applied. Statistical analysis was performed using StataV12. Results Fifty nine patients were included in the study, all but three were adults; 47 (79,6% were male; parasitaemia on admission, quantified in 48/59 (81.3% patients, was equal or greater than 2% in 47 of them (97.9%; the most common complications were thrombocytopaenia in 54 (91.5% patients, associated with disseminated intravascular coagulation (DIC in seven (11.8%, renal failure in 31 (52.5% patients, 18 of which (30.5% oliguric, shock in 29 (49.1% patients, liver dysfunction in 27 (45.7% patients, acidaemia in 23 (38.9% patients, cerebral dysfunction in 22 (37.2% patients, 11 of whom with unrousable coma, pulmonary oedema/ARDS in 22 (37.2% patients, hypoglycaemia in 18 (30.5% patients; 29 (49.1% patients presented five or more dysfunctions. The case fatality rate was 15.2%. Comparing the four scores, the SAPS II and the WHO score were the most sensitive to death prediction. In the univariate analysis, death was associated with the SAPS II score, cerebral malaria, acute renal and respiratory failure, DIC, spontaneous bleeding, acidosis and hypoglycaemia. Age, partial immunity to malaria, delay in malaria diagnosis and the level of parasitaemia were

  5. Differential microRNA expression in experimental cerebral and noncerebral malaria

    DEFF Research Database (Denmark)

    El-Assaad, Fatima; Hempel, Casper; Combes, Valéry

    2011-01-01

    berghei ANKA (PbA), which causes cerebral malaria (CM), or Plasmodium berghei K173 (PbK), which causes severe malaria but without cerebral complications, termed non-CM. The differential expression profiles of selected miRNAs (let-7i, miR-27a, miR-150, miR-126, miR-210, and miR-155) were analyzed in mouse...... acute malaria. To investigate the involvement of let-7i, miR-27a, and miR-150 in CM-resistant mice, we assessed the expression levels in gamma interferon knockout (IFN-¿(-/-)) mice on a C57BL/6 genetic background. The expression of let-7i, miR-27a, and miR-150 was unchanged in both wild-type (WT...... a regulatory role in the pathogenesis of severe malaria....

  6. Depression of platelet counts in apparently healthy children with asymptomatic malaria infection in a Nigerian metropolitan city.

    Science.gov (United States)

    Jeremiah, Zaccheaus Awortu; Uko, Emmanuel Kufre

    2007-09-01

    Asymptomatic malaria infection is a common feature of malaria endemic regions in the tropics. In this prospective cross sectional survey, involving 240 children aged 1 to 8 years (Boys = 117, Girls = 123; Ratio 1:1.05), the median platelet count was 115 x 10(9)/L (IQR 97.5-190). Thirty-three out of 240 (13.75%) of the children had thrombocytopenia (platelet count platelet count. This reduction was more pronounced in children under 5 years and also at higher parasite counts. An inverse relationship was established between parasite density and platelet count (y = -0.017x + 96.2, r = -0.2). Thrombocytopenia is not only a feature of acute malaria infection but also that of asymptomatic malaria infection in the tropics and might be a useful indicator of malaria in children.

  7. Current scenario of malaria vaccine

    Directory of Open Access Journals (Sweden)

    Jarnail Singh Braich

    2012-04-01

    Full Text Available Malaria is one of the deadliest infectious diseases that affects millions of people worldwide including India. As an addition to chemoprophylaxis and other antimalarial interventions malaria vaccine is under extensive research since decades. The vaccine development is more difficult to predict than drug development and presents a unique challenge as already there has been no vaccine effective against a parasite. Effective malaria vaccine could help eliminate and eradicate malaria; there are currently 63 vaccine candidates, 41 in preclinical and clinical stages of development. Vaccines are being designed to target pre-erythrocytic stages, erythrocytic stage or the sexual stages of Plasmodium taken up by a feeding mosquito, or the multiple stages. Two vaccines in preclinical and clinical development target P. falciparum; and the most advanced candidate is the pre-erythrocytic vaccine RTS,S which is in phase-III clinical trials. It is likely that world's first malaria vaccine will be available by 2015 at the country level. More efficacious second generation malaria vaccines are on the way to development. Safety, efficacy, cost and provision of the vaccine to all communities are major concerns in malaria vaccine issue. [Int J Basic Clin Pharmacol 2012; 1(2.000: 60-66

  8. Wild Rodent Ectoparasites Collected from Northwestern Iran

    Directory of Open Access Journals (Sweden)

    Zabihollah Zarei

    2017-04-01

    Full Text Available Background: Rodents play an important role as reservoir of some pathogens, and the host of some ectoparasites as well. These ectoparasites can transmit rodents’ pathogens to human or animals. The aim of this study was to assess the distribution and infestation load of ectoparasites on rodents in Meshkin-Shahr District, northwestern Iran.Method: Rodents were captured using baited live traps in spring 2014 from Meshkin-Shahr District and were trans­ferred to the laboratory for identification to the species level. Their ectoparasites were collected, mounted and identi­fied.Results: Three rodent species including Meriones persicus (74%, Mus musculus (16.9% and Cricetulus migrato­rius (9% were identified. Among all rodents, 185 specimens (90.69% were infested with a total of 521 ectopara­sites. Overall, 10 arthropods species were collected, including fleas (97.6%, one mite (1.6% and one louse species (0.6% as follows: Xenopsylla nubica, X. astia, X. buxtoni, X. cheopis, Nosopsyllus fasciatus, N. iranus, Cten­ocephalides felis, Ctenophthalmus rettigismiti, Ornithonyssus sp and one species of genus Polyplax. The most prev­alent ectoparasites species was X. nubica (89%.Conclusion: Nearly all rodent species were infested with Xenopsylla species. Monitoring of ectoparasites on infested rodents is very important for awareness and early warning towards control of arthropod-borne diseases.

  9. Rodents: food or pests in Neolithic Orkney.

    Science.gov (United States)

    Romaniuk, Andrzej A; Shepherd, Alexandra N; Clarke, David V; Sheridan, Alison J; Fraser, Sheena; Bartosiewicz, László; Herman, Jeremy S

    2016-10-01

    Rodents have important effects on contemporary human societies, sometimes providing a source of food but more often as agricultural pests, or as vectors and reservoirs of disease. Skeletal remains of rodents are commonly found in archaeological assemblages from around the world, highlighting their potential importance to ancient human populations. However, there are few studies of the interactions between people and rodents at such sites and most of these are confined to locations where rodents have formed a part of the recent diet. Here we compare the accumulation pattern of rodent remains from four locations within and adjacent to the renowned Neolithic site of Skara Brae, Orkney, showing that those within the settlement itself were the result of deliberate human activity. The accumulation and nature of burnt bones, incorporated over an extended period within deposits of household waste, indicate that rodents were used as a nutritional resource and may have been the subject of early pest control. We, therefore, provide the first evidence for the exploitation or control of rodents by the Neolithic inhabitants of Europe.

  10. Effects of lime juice on malaria parasite clearance.

    Science.gov (United States)

    Adegoke, S A; Oyelami, O A; Olatunya, O S; Adeyemi, L A

    2011-10-01

    One hundred and twenty children with acute uncomplicated malaria who were managed at the children's outpatient department of the Wesley Guild Hospital, Ilesa (a unit of Obafemi Awolowo University Teaching Hospitals' Complex, Ile-Ife, Osun state, Nigeria) were recruited into the study to determine the effects of lime juice on malaria parasite clearance. These children were randomized into treatment with World Health Organization recommended antimalarials (artemisinin combination therapy, ACT) either alone or with lime juice. Nine of them were lost to follow-up, four were in the group that were managed with ACT and lime, and five in the group that were managed on ACT alone. The average (SD) time to achieve >75% reduction in parasite load was significantly lower in patients on ACT and lime; 30.5 ± 2.4 h against 38.6 ± 3.3 h for those on ACT alone (p lime juice achieved complete parasite clearance by 72 h of therapy (p = 0.007), ten (18.2%) patients without lime had early treatment failure (p = 0.003). There were no side effects with the use of lime juice. It may therefore be inferred, from this preliminary work, that lime juice when used with the appropriate antimalarial may enhance malaria parasite clearance especially in those with uncomplicated malaria.

  11. Malaria haplotype frequency estimation.

    Science.gov (United States)

    Wigger, Leonore; Vogt, Julia E; Roth, Volker

    2013-09-20

    We present a Bayesian approach for estimating the relative frequencies of multi-single nucleotide polymorphism (SNP) haplotypes in populations of the malaria parasite Plasmodium falciparum by using microarray SNP data from human blood samples. Each sample comes from a malaria patient and contains one or several parasite clones that may genetically differ. Samples containing multiple parasite clones with different genetic markers pose a special challenge. The situation is comparable with a polyploid organism. The data from each blood sample indicates whether the parasites in the blood carry a mutant or a wildtype allele at various selected genomic positions. If both mutant and wildtype alleles are detected at a given position in a multiply infected sample, the data indicates the presence of both alleles, but the ratio is unknown. Thus, the data only partially reveals which specific combinations of genetic markers (i.e. haplotypes across the examined SNPs) occur in distinct parasite clones. In addition, SNP data may contain errors at non-negligible rates. We use a multinomial mixture model with partially missing observations to represent this data and a Markov chain Monte Carlo method to estimate the haplotype frequencies in a population. Our approach addresses both challenges, multiple infections and data errors.

  12. Ungulate malaria parasites

    Science.gov (United States)

    Templeton, Thomas J.; Asada, Masahito; Jiratanh, Montakan; Ishikawa, Sohta A.; Tiawsirisup, Sonthaya; Sivakumar, Thillaiampalam; Namangala, Boniface; Takeda, Mika; Mohkaew, Kingdao; Ngamjituea, Supawan; Inoue, Noboru; Sugimoto, Chihiro; Inagaki, Yuji; Suzuki, Yasuhiko; Yokoyama, Naoaki; Kaewthamasorn, Morakot; Kaneko, Osamu

    2016-01-01

    Haemosporida parasites of even-toed ungulates are diverse and globally distributed, but since their discovery in 1913 their characterization has relied exclusively on microscopy-based descriptions. In order to bring molecular approaches to bear on the identity and evolutionary relationships of ungulate malaria parasites, we conducted Plasmodium cytb-specific nested PCR surveys using blood from water buffalo in Vietnam and Thailand, and goats in Zambia. We found that Plasmodium is readily detectable from water buffalo in these countries, indicating that buffalo Plasmodium is distributed in a wider region than India, which is the only area in which buffalo Plasmodium has been reported. Two types (I and II) of Plasmodium sequences were identified from water buffalo and a third type (III) was isolated from goat. Morphology of the parasite was confirmed in Giemsa-reagent stained blood smears for the Type I sample. Complete mitochondrial DNA sequences were isolated and used to infer a phylogeny in which ungulate malaria parasites form a monophyletic clade within the Haemosporida, and branch prior to the clade containing bird, lizard and other mammalian Plasmodium. Thus it is likely that host switching of Plasmodium from birds to mammals occurred multiple times, with a switch to ungulates independently from other mammalian Plasmodium. PMID:26996979

  13. Drug resistance in malaria

    Directory of Open Access Journals (Sweden)

    S C Parija

    2011-01-01

    Full Text Available Antimalarial chemotherapy is an important component of all malaria control programmes throughout the world. This is especially so in light of the fact that there are no antimalarial vaccines which are available for clinical use at present. Emergence and spread of malaria parasites which are resistant to many of the available antimalarials today is, therefore, a major cause for concern. Till date, resistance to all groups of antimalarials excluding artemisinin has been reported. In recent years, in vitro resistance to even artemisinin has been described. While resistance to antibacterial agents has come to prominence as a clinical problem in recent years, antiparasitic resistance in general and antimalarial resistance in particular has not received much attention, especially in the Indian scenario. The present review deals with commonly used antimalarial drugs and the mechanisms of resistance to them. Various methods of detecting antimalarial resistance and avoiding the same have also been dealt with. Newer parasite targets which can be used in developing newer antimalarial agents and antimalarials obtained from plants have also been mentioned.

  14. Malaria-associated peripheral gangrene

    Directory of Open Access Journals (Sweden)

    Deborah B. Martins

    2014-09-01

    Full Text Available Malaria is a common parasitic disease endemic in tropical and subtropical areas, including Mozambique. Symmetrical peripheral gangrene is a rare complication of malaria. The purpose of this study was to review cases of malaria-associated peripheral gangrene that were evaluated by the pediatric surgical service at Hospital Central. Four patients ranging in age from 11 months to 7 years with documented Plasmodium falciparum infection and peripheral gangrene were identified. Amputation was required in cases of wet-gangrene. The majority of cases were allowed to self-demarcate, and one was allowed to auto-amputate.

  15. Glutathione Reductase-null Malaria Parasites Have Normal Blood Stage Growth but Arrest during Development in the Mosquito*

    OpenAIRE

    Pastrana-Mena, Rebecca; Dinglasan, Rhoel R.; Franke-Fayard, Blandine; Vega-Rodríguez, Joel; Fuentes-Caraballo, Mariela; Baerga-Ortiz, Abel; Coppens, Isabelle; Jacobs-Lorena, Marcelo; Janse, Chris J.; Serrano, Adelfa E.

    2010-01-01

    Malaria parasites contain a complete glutathione (GSH) redox system, and several enzymes of this system are considered potential targets for antimalarial drugs. Through generation of a γ-glutamylcysteine synthetase (γ-GCS)-null mutant of the rodent parasite Plasmodium berghei, we previously showed that de novo GSH synthesis is not critical for blood stage multiplication but is essential for oocyst development. In this study, phenotype analyses of mutant parasites lacking expression of glutath...

  16. A rapid and robust selection procedure for generating drug-selectable marker-free recombinant malaria parasites

    OpenAIRE

    2014-01-01

    International audience; Experimental genetics have been widely used to explore the biology of the malaria parasites. The rodent parasites Plasmodium berghei and less frequently P. yoelii are commonly utilised, as their complete life cycle can be reproduced in the laboratory and because they are genetically tractable via homologous recombination. However, due to the limited number of drug-selectable markers, multiple modifications of the parasite genome are difficult to achieve and require lar...

  17. HIV treatments reduce malaria liver stage burden in a non-human primate model of malaria infection at clinically relevant concentrations in vivo.

    Directory of Open Access Journals (Sweden)

    Charlotte V Hobbs

    Full Text Available We have previously shown that the HIV protease inhibitor lopinavir-ritonavir (LPV-RTV and the antibiotic trimethoprim sulfamethoxazole (TMP-SMX inhibit Plasmodium liver stages in rodent malarias and in vitro in P. falciparum. Since clinically relevant levels are better achieved in the non-human-primate model, and since Plasmodium knowlesi is an accepted animal model for the study of liver stages of malaria as a surrogate for P. falciparum infection, we investigated the antimalarial activity of these drugs on Plasmodium knowlesi liver stages in rhesus macaques. We demonstrate that TMP-SMX and TMP-SMX+LPV-RTV (in combination, but not LPV-RTV alone, inhibit liver stage parasite development. Because drugs that inhibit the clinically silent liver stages target parasites when they are present in lower numbers, these results may have implications for eradication efforts.

  18. Type I interferon transcriptional signature in neutrophils and high frequency of low-density granulocytes are associated with tissue damage in malaria

    Science.gov (United States)

    Rocha, Bruno Coelho; Marques, Pedro Elias; Leoratti, Fabiana Maria de Souza; Junqueira, Caroline; Pereira, Dhelio Batista; Antonelli, Lis Ribeiro do Valle; Menezes, Gustavo Batista

    2015-01-01

    SUMMARY Neutrophils are the most abundant leukocyte population in the bloodstream, the primary compartment of Plasmodium sp. infection. Yet, the role of these polymorphonuclear cells in mediating either resistance or pathogenesis of malaria is poorly understood. We report that circulating neutrophils from malaria patients are highly activated, as indicated by a strong type I interferon transcriptional signature, increased expression of surface activation markers, the enhanced release of reactive oxygen species and myeloperoxidase, as well as the high frequency of low-density granulocytes. The activation of neutrophils was associated with increased levels of serum alanine and aspartate aminotransferases, indicating liver damage. In a rodent malaria model, we observed an intense recruitment of neutrophils to liver sinusoids. Neutrophil migration, IL-1β and chemokine expression as well as liver damage were all dependent on type I interferon signaling. The data suggests that type I interferon signaling have a central role in neutrophil activation and malaria pathogenesis. PMID:26711347

  19. Historical Review: Problematic Malaria Prophylaxis with Quinine.

    Science.gov (United States)

    Shanks, G Dennis

    2016-08-03

    Quinine, a bitter-tasting, short-acting alkaloid drug extracted from cinchona bark, was the first drug used widely for malaria chemoprophylaxis from the 19th century. Compliance was difficult to enforce even in organized groups such as the military, and its prophylaxis potential was often questioned. Severe adverse events such as blackwater fever occurred rarely, but its relationship to quinine remains uncertain. Quinine prophylaxis was often counterproductive from a public health viewpoint as it left large numbers of persons with suppressed infections producing gametocytes infective for mosquitoes. Quinine was supplied by the first global pharmaceutical cartel which discouraged competition resulting in a near monopoly of cinchona plantations on the island of Java which were closed to Allied use when the Japanese Imperial Army captured Indonesia in 1942. The problems with quinine as a chemoprophylactic drug illustrate the difficulties with medications used for prevention and the acute need for improved compounds.

  20. Whole blood angiopoietin-1 and -2 levels discriminate cerebral and severe (non-cerebral malaria from uncomplicated malaria

    Directory of Open Access Journals (Sweden)

    Tangpukdee Noppadon

    2009-12-01

    Full Text Available Abstract Background Severe and cerebral malaria are associated with endothelial activation. Angiopoietin-1 (ANG-1 and angiopoietin-2 (ANG-2 are major regulators of endothelial activation and integrity. The aim of this study was to investigate the clinical utility of whole blood angiopoietin (ANG levels as biomarkers of disease severity in Plasmodium falciparum malaria. Methods The utility of whole blood ANG levels was examined in Thai patients to distinguish cerebral (CM; n = 87 and severe (non-cerebral malaria (SM; n = 36 from uncomplicated malaria (UM; n = 70. Comparative statistics are reported using a non-parametric univariate analysis (Kruskal-Wallis test or Chi-squared test, as appropriate. Multivariate binary logistic regression was used to examine differences in whole blood protein levels between groups (UM, SM, CM, adjusting for differences due to ethnicity, age, parasitaemia and sex. Receiver operating characteristic curve analysis was used to assess the diagnostic accuracy of the ANGs in their ability to distinguish between UM, SM and CM. Cumulative organ injury scores were obtained for patients with severe disease based on the presence of acute renal failure, jaundice, severe anaemia, circulatory collapse or coma. Results ANG-1 and ANG-2 were readily detectable in whole blood. Compared to UM there were significant decreases in ANG-1 (p Conclusions These results suggest that whole blood ANG-1/2 levels are promising clinically informative biomarkers of disease severity in malarial syndromes.

  1. Chronic malaria revealed by a new fluorescence pattern on the antinuclear autoantibodies test.

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    Benjamin Hommel

    Full Text Available BACKGROUND: Several clinical forms of malaria such as chronic carriage, gestational malaria or hyper-reactive malarial splenomegaly may follow a cryptic evolution with afebrile chronic fatigue sometimes accompanied by anemia and/or splenomegaly. Conventional parasitological tests are often negative or not performed, and severe complications may occur. Extensive explorations of these conditions often include the search for antinuclear autoantibodies (ANA. METHODS: We analysed fluorescence patterns in the ANA test in patients with either chronic cryptic or acute symptomatic malaria, then conducted a one-year prospective study at a single hospital on all available sera drawn for ANA detections. We then identified autoantibodies differentially expressed in malaria patients and in controls using human protein microarray. RESULTS: We uncovered and defined a new, malaria-related, nucleo-cytoplasmic ANA pattern displaying the specific association of a nuclear speckled pattern with diffuse cytoplasmic perinuclearly-enhanced fluorescence. In the one-year prospective analysis, 79% of sera displaying this new nucleo-cytoplasmic fluorescence were from patients with malaria. This specific pattern, not seen in other parasitic diseases, allowed a timely reorientation of the diagnosis toward malaria. To assess if the autoantibody immune response was due to autoreactivity or molecular mimicry we isolated 42 autoantigens, targets of malarial autoantibodies. BLAST analysis indicated that 23 of recognized autoantigens were homologous to plasmodial proteins suggesting autoimmune responses directly driven by the plasmodial infection. CONCLUSION: In patients with malaria in whom parasitological tests have not been performed recognition of this new, malaria-related fluorescence pattern on the ANA test is highly suggestive of the diagnosis and triggers immediate, easy confirmation and adapted therapy.

  2. Study of clinical presentation of malaria and the associated liver profile changes in various species of plasmodia

    Directory of Open Access Journals (Sweden)

    Siddanagouda M. Biradar

    2016-12-01

    Conclusions: Malaria is a potential cause of morbidity and mortality in the tropical countries. Jaundice is one of the common presentations of falciparum malaria. The raised serum bilirubin could be due to both hemolysis and hepatocellular dysfunction. Early diagnosis and treatment will help in reducing further complications like severe anaemia, hepatic encephalopathy, acute renal failure and disseminated intravascular coagulation. [Int J Res Med Sci 2016; 4(12.000: 5447-5451

  3. Preliminary study of quinine pharmacokinetics in pregnant women with malaria-HIV co-infection.

    Science.gov (United States)

    Kayentao, Kassoum; Guirou, Etienne A; Doumbo, Ogobara K; Venkatesan, Meera; Plowe, Christopher V; Parsons, Teresa L; Hendrix, Craig W; Nyunt, Myaing M

    2014-03-01

    Pregnant women bear the greatest burden of malaria-human immunodeficiency virus co-infection. Previous studies suggest that interaction with antiretroviral drugs may compromise antimalarial pharmacokinetics and treatment outcomes. We conducted a preliminary clinical study to assess quinine pharmacokinetics in Malian pregnant women with acute malaria who reported taking nevirapine-based antiretroviral therapy. Of seven women, six had stable concentrations of nevirapine in the plasma and one had none. Quinine concentrations were lower, and its metabolite 3-hydroxyquinine higher, in the six women with nevirapine than in the one without, and quinine concentrations were below the recommended therapeutic range in 50% of the women. This preliminary observation warrants further research to understand the impact of long-term antiretroviral therapy on the treatment of acute malaria.

  4. TRALI Syndrome During the Treatment of a Plasmodium falciparum Malaria Case.

    Science.gov (United States)

    Çaşkurlu, Hülya; Nurmuhammedov, Rahman; Htway, Zarni

    2016-12-01

    Malaria, which is one of the three most important infectious diseases globally, is endemic in many areas of the world. Plasmodium falciparum is not endemic to Turkey but can be seen after travel to epidemic countries. Transfusion-related acute lung injury (TRALI) syndrome is a rare disease, which may develop following the transfusion of all types of blood products, including plasma. Here we describe a case of TRALI syndrome in a 29-year-old male, who presented with fever after 15 days of returning from a business trip to Burkina Faso. It developed immediately after the infusion of fresh frozen plasma during the treatment of P. falciparum malaria. The patient's condition improved on respiratory support treatment in the intensive care unit for 48 hours without the need of mechanical ventilation. This case indicated that TRALI syndrome has to be considered in the differential diagnosis as an emerging acute lung disease during the treatment of malaria.

  5. Modeling panic disorder in rodents.

    Science.gov (United States)

    Moreira, Fabrício A; Gobira, Pedro H; Viana, Thércia G; Vicente, Maria A; Zangrossi, Hélio; Graeff, Frederico G

    2013-10-01

    Panic disorder (PD) is a subtype of anxiety disorder in which the core phenomenon is the spontaneous occurrence of panic attacks. Although studies with laboratory animals have been instrumental for the understanding of its neurobiology and treatment, few review articles have focused on the validity of the currently used animal models for studying this psychopathology. Therefore, the aim of the present paper is to discuss the strengths and limits of these models in terms of face, construct and predictive validity. Based on the hypothesis that panic attacks are related to defensive responses elicited by proximal threat, most animal models measure the escape responses induced by specific stimuli. Some apply electrical or chemical stimulation to brain regions proposed to modulate fear and panic responses, such as the dorsal periaqueductal grey or the medial hypothalamus. Other models focus on the behavioural consequences caused by the exposure of rodents to ultrasound or natural predators. Finally, the elevated T-maze associates a one-way escape response from an open arm with panic attacks. Despite some limitations, animal models are essential for a better understanding of the neurobiology and pharmacology of PD and for discovering more effective treatments.

  6. Malaria ecology and climate change

    Science.gov (United States)

    McCord, G. C.

    2016-05-01

    Understanding the costs that climate change will exact on society is crucial to devising an appropriate policy response. One of the channels through while climate change will affect human society is through vector-borne diseases whose epidemiology is conditioned by ambient ecology. This paper introduces the literature on malaria, its cost on society, and the consequences of climate change to the physics community in hopes of inspiring synergistic research in the area of climate change and health. It then demonstrates the use of one ecological indicator of malaria suitability to provide an order-of-magnitude assessment of how climate change might affect the malaria burden. The average of Global Circulation Model end-of-century predictions implies a 47% average increase in the basic reproduction number of the disease in today's malarious areas, significantly complicating malaria elimination efforts.

  7. ENVIRONMENTAL MANAGEMENT FOR MALARIA CONTROL

    Directory of Open Access Journals (Sweden)

    H. A. Rafatjah

    1976-09-01

    Full Text Available Environmental management for malaria control is defined as any planned physical activities that through transformation of land, water and vegetation will result in the prevention, reduction or elimination of malaria. In planning and implementing these activities, full consideration must be given to their long-term effects and benefits and to the preservation of the quality of environment and they need to be fully and closely coordinated with water, land and agricultural development projects. Environmental management activities for malaria control can be classified as source reduction, dealing mainly with physical alteration of the environment; environmental manipulation, introducing temporary environmental changes and the reduction, and prevention of man-vector contact by site selection, mosquito proofing of dwellings and personal protection. For anti-malaria programs to employ these activities they need to re-train the staff, re-orient the services and set up pilot operations for feasibility studies.

  8. Premunition in Plasmodium falciparum malaria

    African Journals Online (AJOL)

    STORAGESEVER

    2010-03-08

    Mar 8, 2010 ... parasite, premunition is probably caused by antitoxic immunity. These poor and ... immunity to clinical malaria rather than infection may be of long duration ... use of antimalaria drugs and its possible strategic role in vaccine ...

  9. Tumor Necrosis Factor-α sebagai Prediktor Terjadinya Anemia pada Ibu Hamil di Wilayah Endemis Malaria

    Directory of Open Access Journals (Sweden)

    Rostika Flora

    2015-04-01

    acute malaria that hinders occurence eritropoesis process. This study aimed to find out relations between TNF-α level and anemia occurrence among pregnant women living in malaria vivax - endemic areas. The study used cross-sectional design conducted on January to February 2014 in five working areas in Bengkulu city. Sample of study was pregnant mothers in malaria vivax - endemic areas which was taken through accidental sampling. Blood was taken for malaria-microscopic examination, TNF-α and haemoglobine (Hb level. The results showed that all of pregnant mothers have malaria vivax - infected record, although slide examination showed negative result. Any TNF-α level elevation with average 6.90 ± 2.48 pg/mL and decrease of Hb level with average 9.75 ± 0.88 g%. Spearman correlation test showed strong negative correlation (r = -0.734 and significant (p value < 0.05 between TNF-α level and Hb level. There was significant relation between TNF-α level and anemia occurrence.

  10. Rodent models of ischemic stroke lack translational relevance... are baboon models the answer?

    Science.gov (United States)

    Kwiecien, Timothy D; Sy, Christopher; Ding, Yuchuan

    2014-05-01

    Rodent models of ischemic stroke are associated with many issues and limitations, which greatly diminish the translational potential of these studies. Recent studies demonstrate that significant differences exist between rodent and human ischemic stroke. These differences include the physical characteristics of the stroke, as well as changes in the subsequent inflammatory and molecular pathways following the acute ischemic insult. Non-human primate (NHP) models of ischemic stroke, however, are much more similar to humans. In addition to evident anatomical similarities, the physiological responses that NHPs experience during ischemic stroke are much more applicable to the human condition and thus make it an attractive model for future research. The baboon ischemic stroke model, in particular, has been studied extensively in comparison to other NHP models. Here we discuss the major shortcomings associated with rodent ischemic stroke models and provide a comparative overview of baboon ischemic stroke models. Studies have shown that baboons, although more difficult to obtain and handle, are more representative of ischemic events in humans and may have greater translational potential that can offset these deficiencies. There remain critical issues within these baboon stroke studies that need to be addressed in future investigations. The most critical issue revolves around the size and the variability of baboon ischemic stroke. Compared to rodent models, however, issues such as these can be addressed in future studies. Importantly, baboon models avoid many drawbacks associated with rodent models including vascular variability and inconsistent inflammatory responses - issues that are inherent to the species and cannot be avoided.

  11. Anatomical and nutritional adaptations in African rodents

    African Journals Online (AJOL)

    retention time suggest that little ruminant-like fibre digestion occurs in the ... gastro-intestinal tract of rodents (Vorontsov, 1962;. Carleton ... and swollen cells superficially. The fornical .... The ways of food specialization and the evolution of the ...

  12. The March Toward Malaria Vaccines

    Science.gov (United States)

    Hoffman, Stephen L.; Vekemans, Johan; Richie, Thomas L.; Duffy, Patrick E.

    2016-01-01

    In 2013 there were an estimated 584,000 deaths and 198 million clinical illnesses due to malaria, the majority in sub-Saharan Africa. Vaccines would be the ideal addition to the existing armamentarium of anti-malaria tools. However, malaria is caused by parasites, and parasites are much more complex in terms of their biology than the viruses and bacteria for which we have vaccines, passing through multiple stages of development in the human host, each stage expressing hundreds of unique antigens. This complexity makes it more difficult to develop a vaccine for parasites than for viruses and bacteria, since an immune response targeting one stage may not offer protection against a later stage, because different antigens are the targets of protective immunity at different stages. Furthermore, depending on the life cycle stage and whether the parasite is extra- or intra-cellular, antibody and/or cellular immune responses provide protection. It is thus not surprising that there is no vaccine on the market for prevention of malaria, or any human parasitic infection. In fact, no vaccine for any disease with this breadth of targets and immune responses exists. In this limited review, we focus on four approaches to malaria vaccines, (1) a recombinant protein with adjuvant vaccine aimed at Plasmodium falciparum (Pf) pre-erythrocytic stages of the parasite cycle (RTS,S/AS01), (2) whole sporozoite vaccines aimed at Pf pre-erythrocytic stages (PfSPZ Vaccine and PfSPZ-CVac), (3) prime boost vaccines that include recombinant DNA, viruses and bacteria, and protein with adjuvant aimed primarily at Pf pre-erythrocytic, but also asexual erythrocytic stages, and (4) recombinant protein with adjuvant vaccines aimed at Pf and Plasmodium vivax sexual erythrocytic and mosquito stages. We recognize that we are not covering all approaches to malaria vaccine development, or most of the critically important work on development of vaccines against P. vivax, the second most important cause of

  13. The march toward malaria vaccines.

    Science.gov (United States)

    Hoffman, Stephen L; Vekemans, Johan; Richie, Thomas L; Duffy, Patrick E

    2015-11-27

    In 2013 there were an estimated 584,000 deaths and 198 million clinical illnesses due to malaria, the majority in sub-Saharan Africa. Vaccines would be the ideal addition to the existing armamentarium of anti-malaria tools. However, malaria is caused by parasites, and parasites are much more complex in terms of their biology than the viruses and bacteria for which we have vaccines, passing through multiple stages of development in the human host, each stage expressing hundreds of unique antigens. This complexity makes it more difficult to develop a vaccine for parasites than for viruses and bacteria, since an immune response targeting one stage may not offer protection against a later stage, because different antigens are the targets of protective immunity at different stages. Furthermore, depending on the life cycle stage and whether the parasite is extra- or intra-cellular, antibody and/or cellular immune responses provide protection. It is thus not surprising that there is no vaccine on the market for prevention of malaria, or any human parasitic infection. In fact, no vaccine for any disease with this breadth of targets and immune responses exists. In this limited review, we focus on four approaches to malaria vaccines, (1) a recombinant protein with adjuvant vaccine aimed at Plasmodium falciparum (Pf) pre-erythrocytic stages of the parasite cycle (RTS,S/AS01), (2) whole sporozoite vaccines aimed at Pf pre-erythrocytic stages (PfSPZ Vaccine and PfSPZ-CVac), (3) prime boost vaccines that include recombinant DNA, viruses and bacteria, and protein with adjuvant aimed primarily at Pf pre-erythrocytic, but also asexual erythrocytic stages, and (4) recombinant protein with adjuvant vaccines aimed at Pf and Plasmodium vivax sexual erythrocytic and mosquito stages. We recognize that we are not covering all approaches to malaria vaccine development, or most of the critically important work on development of vaccines against P. vivax, the second most important cause of

  14. Decline of FoxP3+ Regulatory CD4 T Cells in Peripheral Blood of Children Heavily Exposed to Malaria.

    Directory of Open Access Journals (Sweden)

    Michelle J Boyle

    2015-07-01

    Full Text Available FoxP3+ regulatory CD4 T cells (Tregs help to maintain the delicate balance between pathogen-specific immunity and immune-mediated pathology. Prior studies suggest that Tregs are induced by P. falciparum both in vivo and in vitro; however, the factors influencing Treg homeostasis during acute and chronic infections, and their role in malaria immunopathogenesis, remain unclear. We assessed the frequency and phenotype of Tregs in well-characterized cohorts of children residing in a region of high malaria endemicity in Uganda. We found that both the frequency and absolute numbers of FoxP3+ Tregs in peripheral blood declined markedly with increasing prior malaria incidence. Longitudinal measurements confirmed that this decline occurred only among highly malaria-exposed children. The decline of Tregs from peripheral blood was accompanied by reduced in vitro induction of Tregs by parasite antigen and decreased expression of TNFR2 on Tregs among children who had intense prior exposure to malaria. While Treg frequencies were not associated with protection from malaria, there was a trend toward reduced risk of symptomatic malaria once infected with P. falciparum among children with lower Treg frequencies. These data demonstrate that chronic malaria exposure results in altered Treg homeostasis, which may impact the development of antimalarial immunity in naturally exposed populations.

  15. Heritability of malaria in Africa.

    Directory of Open Access Journals (Sweden)

    Margaret J Mackinnon

    2005-12-01

    Full Text Available While many individual genes have been identified that confer protection against malaria, the overall impact of host genetics on malarial risk remains unknown.We have used pedigree-based genetic variance component analysis to determine the relative contributions of genetic and other factors to the variability in incidence of malaria and other infectious diseases in two cohorts of children living on the coast of Kenya. In the first, we monitored the incidence of mild clinical malaria and other febrile diseases through active surveillance of 640 children 10 y old or younger, living in 77 different households for an average of 2.7 y. In the second, we recorded hospital admissions with malaria and other infectious diseases in a birth cohort of 2,914 children for an average of 4.1 y. Mean annual incidence rates for mild and hospital-admitted malaria were 1.6 and 0.054 episodes per person per year, respectively. Twenty-four percent and 25% of the total variation in these outcomes was explained by additively acting host genes, and household explained a further 29% and 14%, respectively. The haemoglobin S gene explained only 2% of the total variation. For nonmalarial infections, additive genetics explained 39% and 13% of the variability in fevers and hospital-admitted infections, while household explained a further 9% and 30%, respectively.Genetic and unidentified household factors each accounted for around one quarter of the total variability in malaria incidence in our study population. The genetic effect was well beyond that explained by the anticipated effects of the haemoglobinopathies alone, suggesting the existence of many protective genes, each individually resulting in small population effects. While studying these genes may well provide insights into pathogenesis and resistance in human malaria, identifying and tackling the household effects must be the more efficient route to reducing the burden of disease in malaria-endemic areas.

  16. Heritability of Malaria in Africa.

    Directory of Open Access Journals (Sweden)

    2005-11-01

    Full Text Available BACKGROUND: While many individual genes have been identified that confer protection against malaria, the overall impact of host genetics on malarial risk remains unknown. METHODS AND FINDINGS: We have used pedigree-based genetic variance component analysis to determine the relative contributions of genetic and other factors to the variability in incidence of malaria and other infectious diseases in two cohorts of children living on the coast of Kenya. In the first, we monitored the incidence of mild clinical malaria and other febrile diseases through active surveillance of 640 children 10 y old or younger, living in 77 different households for an average of 2.7 y. In the second, we recorded hospital admissions with malaria and other infectious diseases in a birth cohort of 2,914 children for an average of 4.1 y. Mean annual incidence rates for mild and hospital-admitted malaria were 1.6 and 0.054 episodes per person per year, respectively. Twenty-four percent and 25% of the total variation in these outcomes was explained by additively acting host genes, and household explained a further 29% and 14%, respectively. The haemoglobin S gene explained only 2% of the total variation. For nonmalarial infections, additive genetics explained 39% and 13% of the variability in fevers and hospital-admitted infections, while household explained a further 9% and 30%, respectively. CONCLUSION: Genetic and unidentified household factors each accounted for around one quarter of the total variability in malaria incidence in our study population. The genetic effect was well beyond that explained by the anticipated effects of the haemoglobinopathies alone, suggesting the existence of many protective genes, each individually resulting in small population effects. While studying these genes may well provide insights into pathogenesis and resistance in human malaria, identifying and tackling the household effects must be the more efficient route to reducing the burden

  17. DNA Sensors for Malaria Diagnosis

    DEFF Research Database (Denmark)

    Hede, Marianne Smedegaard; Fjelstrup, Søren; Knudsen, Birgitta R.

    2015-01-01

    In the field of malaria diagnosis much effort is put into the development of faster and easier alternatives to the gold standard, blood smear microscopy. Nucleic acid amplification based techniques pose some of the most promising upcoming diagnostic tools due to their potential for high sensitivi......, robustness and user-friendliness. In the current review, we will discuss some of the different DNA-based sensor systems under development for the diagnosis of malaria....

  18. Imported malaria in Okayama prefecture

    OpenAIRE

    安治, 敏樹; 頓宮, 廉正; 頼, 俊雄; 何, 黎星; 下野, 國夫; 稲臣, 成一; 村主,節雄; 塩田, 哲也; 桜井, 浩一

    1981-01-01

    Two cases of imported malaria which occurred in Okayama prefecture are reported. One was infected with Plasmodium vivax in India, the other with P. falciparum at Nigeria, Africa. The efficacy of some antimalarial drugs in these cases is discussed. One patient was infected with P. falciparum, despite taking the medicine Daraprim® regularly. The efficacy of Daraprim® for suppressive cure in Nigeria is doutful. The therapy of chloroquine-resistance tropical malaria is also discussed.

  19. Rodent phylogeny revised: analysis of six nuclear genes from all major rodent clades

    Directory of Open Access Journals (Sweden)

    Pupko Tal

    2009-04-01

    Full Text Available Abstract Background Rodentia is the most diverse order of placental mammals, with extant rodent species representing about half of all placental diversity. In spite of many morphological and molecular studies, the family-level relationships among rodents and the location of the rodent root are still debated. Although various datasets have already been analyzed to solve rodent phylogeny at the family level, these are difficult to combine because they involve different taxa and genes. Results We present here the largest protein-coding dataset used to study rodent relationships. It comprises six nuclear genes, 41 rodent species, and eight outgroups. Our phylogenetic reconstructions strongly support the division of Rodentia into three clades: (1 a "squirrel-related clade", (2 a "mouse-related clade", and (3 Ctenohystrica. Almost all evolutionary relationships within these clades are also highly supported. The primary remaining uncertainty is the position of the root. The application of various models and techniques aimed to remove non-phylogenetic signal was unable to solve the basal rodent trifurcation. Conclusion Sequencing and analyzing a large sequence dataset enabled us to resolve most of the evolutionary relationships among Rodentia. Our findings suggest that the uncertainty regarding the position of the rodent root reflects the rapid rodent radiation that occurred in the Paleocene rather than the presence of conflicting phylogenetic and non-phylogenetic signals in the dataset.

  20. Estimating head and body length in fossil rodents

    NARCIS (Netherlands)

    Freudenthal, M.; Martín-Suárez, E.

    2015-01-01

    We present estimates for head and body length (HBL) of fossil rodents. We assembled HBL data and tooth row length data (LTR, UTR) for a large number of extant rodents, and calculated regression lines of HBL on LTR and UTR for all rodents together (all-rodents equation), and for separate taxonomic gr

  1. Convergent and Divergent Adaptations of Subterranean Rodents

    DEFF Research Database (Denmark)

    Fang, Xiaodong

    Subterranean rodents comprise approximately 250 species that spend their entire lives in underground, unventilated tunnels, distributed along all continents except Australia and Antarctica. Subterranean rodents escape from predators and extreme climatic fluctuations in their underground habitats,......, coupled with the reported genetic information, will promote the utilization of subterranean animal models for biological and biomedical research in the fight against aging, cancer, stroke and other realted diseases....

  2. Acute Blast Injury Reduces Brain Abeta in Two Rodent Species

    Science.gov (United States)

    2012-12-01

    De Gasperi 1,2,3, Miguel A. Gama Sosa1,2,3, Soong Ho Kim4, John W. Steele4,5, Michael C. Shaughness6, Eric Maudlin-Jeronimo6, Aaron A. Hall 6...Wetzlar, Ger- many). Immunohistochemical staining was performed as previ- ously described ( Gama Sosa et al., 2010) using a rabbit anti-APP antibody APP369...Traumatic brain injury: football, warfare, and long- term effects. N. Engl. J. Med. 363, 1293–1296. Elder, G. A., Dorr, N. P., De Gasperi, R., Gama Sosa, M. A

  3. Rodents as potential couriers for bioterrorism agents.

    Science.gov (United States)

    Lõhmus, Mare; Janse, Ingmar; van de Goot, Frank; van Rotterdam, Bart J

    2013-09-01

    Many pathogens that can cause major public health, economic, and social damage are relatively easily accessible and could be used as biological weapons. Wildlife is a natural reservoir for many potential bioterrorism agents, and, as history has shown, eliminating a pathogen that has dispersed among wild fauna can be extremely challenging. Since a number of wild rodent species live close to humans, rodents constitute a vector for pathogens to circulate among wildlife, domestic animals, and humans. This article reviews the possible consequences of a deliberate spread of rodentborne pathogens. It is relatively easy to infect wild rodents with certain pathogens or to release infected rodents, and the action would be difficult to trace. Rodents can also function as reservoirs for diseases that have been spread during a bioterrorism attack and cause recurring disease outbreaks. As rats and mice are common in both urban and rural settlements, deliberately released rodentborne infections have the capacity to spread very rapidly. The majority of pathogens that are listed as potential agents of bioterrorism by the Centers for Disease Control and Prevention and the National Institute of Allergy and Infectious Diseases exploit rodents as vectors or reservoirs. In addition to zoonotic diseases, deliberately released rodentborne epizootics can have serious economic consequences for society, for example, in the area of international trade restrictions. The ability to rapidly detect introduced diseases and effectively communicate with the public in crisis situations enables a quick response and is essential for successful and cost-effective disease control.

  4. Establishing Primary Adult Fibroblast Cultures From Rodents

    Science.gov (United States)

    Seluanov, Andrei; Vaidya, Amita; Gorbunova, Vera

    2010-01-01

    The importance of using primary cells, rather than cancer cell lines, for biological studies is becoming widely recognized. Primary cells are preferred in studies of cell cycle control, apoptosis, and DNA repair, as cancer cells carry mutations in genes involved in these processes. Primary cells cannot be cultured indefinitely due to the onset of replicative senescence or aneuploidization. Hence, new cultures need to be established regularly. The procedure for isolation of rodent embryonic fibroblasts is well established, but isolating adult fibroblast cultures often presents a challenge. Adult rodent fibroblasts isolated from mouse models of human disease may be a preferred control when comparing them to fibroblasts from human patients. Furthermore, adult fibroblasts are the only available material when working with wild rodents where pregnant females cannot be easily obtained. Here we provide a protocol for isolation and culture of adult fibroblasts from rodent skin and lungs. We used this procedure successfully to isolate fibroblasts from over twenty rodent species from laboratory mice and rats to wild rodents such as beaver, porcupine, and squirrel. PMID:20972406

  5. Interleukin-10 regulates hepcidin in Plasmodium falciparum malaria

    KAUST Repository

    Huang, Honglei

    2014-02-10

    Background: Acute malarial anemia remains a major public health problem. Hepcidin, the major hormone controlling the availability of iron, is raised during acute and asymptomatic parasitemia. Understanding the role and mechanism of raised hepcidin and so reduced iron availability during infection is critical to establish evidence-based guidelines for management of malaria anemia. Our recent clinical evidence suggests a potential role of IL-10 in the regulation of hepcidin in patients with acute P. falciparum malaria. Methods: We have measured secretion of hepcidin by primary macrophages and the hepatoma cell line HepG2 stimulated with IL-10, IL-6 and Plasmodium falciparum-infected erythrocytes. Findings: We have observed that IL-10 and IL-6 production increased in primary macrophages when these cells were co-cultured with Plasmodium falciparum-infected erythrocytes. We found that IL-10 induced hepcidin secretion in primary macrophages in a dose-dependent manner but not in HepG2 cells. These effects were mediated through signal transducer and activator of transcription (STAT) 3-phosphorylation and completely abrogated by a specific STAT3 inhibitor. Conclusion: IL-10 can directly regulate hepcidin in primary macrophages but not in HepG2 cells. This effect can be modulated by Plasmodium falciparum. The results are consistent with a role for IL-10 in modulating iron metabolism during acute phase of infection. 2014 Huang et al.

  6. Muscling out malaria

    DEFF Research Database (Denmark)

    Hughes, David Peter; Boomsma, Jacobus Jan

    2006-01-01

    Recent updates in Trends in Parasitology [1] and Trends in Ecology and Evolution 2 R.H. ffrench-Constant, Something old, something transgenic, or something fungal for mosquito control?, Trends Ecol. Evol. 20 (2005), pp. 577-579. Article | PDF (122 K) | View Record in Scopus | Cited By in Scopus (3......) [2] highlighted the back-to-back articles in Science 3 and 4 that demonstrated the potential biocontrol of malaria by targeting mosquitoes with entomopathogenic fungi (Metarhizium and Beauveria spp.). The wide impact of the original articles and the need to find alternatives to pesticidal control...... are likely to encourage the incorporation of these fungi into biocontrol programs, although several concerns have been raised 1 , 2 and 5 . Here, we detail some of these and advocate an inclusive approach to malarial biocontrol that proceeds with a full appreciation of the complicated biology...

  7. Neuronal apoptosis, metallothionein expression and proinflammatory responses during cerebral malaria in mice

    DEFF Research Database (Denmark)

    Wiese, Lothar; Kurtzhals, Jørgen A L; Penkowa, Milena

    2006-01-01

    BACKGROUND: Cerebral malaria (CM) is an acute encephalopathy in humans due to the infection with Plasmodium falciparum. Neuro-cognitive impairment following CM occurs in about 10% of the treated survivors, while the precise pathophysiological mechanism remains unknown. Metallothionein I + II (MT-...

  8. Reduced erythrocyte deformability associated with hypoargininemia during Plasmodium falciparum malaria.

    Science.gov (United States)

    Rey, Juliana; Buffet, Pierre A; Ciceron, Liliane; Milon, Geneviève; Mercereau-Puijalon, Odile; Safeukui, Innocent

    2014-01-20

    The mechanisms underlying reduced red blood cell (RBC) deformability during Plasmodium falciparum (Pf) malaria remain poorly understood. Here, we explore the possible involvement of the L-arginine and nitric oxide (NO) pathway on RBC deformability in Pf-infected patients and parasite cultures. RBC deformability was reduced during the acute attack (day0) and returned to normal values upon convalescence (day28). Day0 values correlated with plasma L-arginine levels (r = 0.69; p = 0.01) and weakly with parasitemia (r = -0.38; p = 0.006). In vitro, day0 patient's plasma incubated with ring-stage cultures at 41°C reduced RBC deformability, and this effect correlated strongly with plasma L-arginine levels (r = 0.89; p falciparum malaria may altogether impair NO production and reduce RBC deformability, particularly at febrile temperature.

  9. [Current malaria situation in Turkey].

    Science.gov (United States)

    Gockchinar, T; Kalipsi, S

    2001-01-01

    Geographically, Turkey is situated in an area where malaria is very risky. The climatic conditions in the region are suitable for the malaria vector to proliferate. Due to agricultural infrastructural changes, GAP and other similar projects, insufficient environmental conditions, urbanization, national and international population moves, are a key to manage malaria control activities. It is estimated that malaria will be a potential danger for Turkey in the forthcoming years. The disease is located largely in south-eastern Anatolia. The Diyarbakir, Batman, Sanliurfa, Siirt, and Mardin districts are the most affected areas. In western districts, like Aydin and Manisa, an increase in the number of indigenous cases can be observed from time to time. This is due to workers moving from malaria districts to western parts to final work. Since these workers cannot be controlled, the population living in these regions get infected from indigenous cases. There were 84,345 malaria cases in 1994 and 82,096 in 1995, they decreased to 60,884 in 1996 and numbered 35,456 in 1997. They accounted for 36,842 and 20,963 in 1998 and 1999, respectively. In Turkey there are almost all cases of P. vivax malaria. There are also P. vivax and P. falciparum malaria cases coming from other countries: There were 321 P. vivax cases, including 2 P. falciparum ones, arriving to Turkey from Iraq in 1995. The P. vivax malaria cases accounted for 229 in 1996, and 67, cases P. vivax including 12 P. falciparum cases, in 1997, and 4 P. vivax cases in 1998 that came from that country. One P. vivax case entered Turkey from Georgia in 1998. The cause of higher incidence of P. vivax cases in 1995, it decreasing in 1999, is the lack of border controls over workers coming to Turkey. The other internationally imported cases are from Syria, Sudan, Pakistan, Afghanistan, Nigeria, India, Azerbaijan, Malaysia, Ghana, Indonesia, Yemen. Our examinations have shown that none of these internationally imported cases

  10. Efficacy and safety of fixed dose combination of arterolane maleate and piperaquine phosphate dispersible tablets in paediatric patients with acute uncomplicated Plasmodium falciparum malaria: a phase II, multicentric, open-label study.

    Science.gov (United States)

    Toure, Offianan Andre; Rulisa, Stephen; Anvikar, Anupkumar R; Rao, Ballamudi S; Mishra, Pitabas; Jalali, Rajinder K; Arora, Sudershan; Roy, Arjun; Saha, Nilanjan; Iyer, Sunil S; Sharma, Pradeep; Valecha, Neena

    2015-11-25

    The World Health Organization (WHO) recommends artemisinin combination therapy (ACT) for the treatment of uncomplicated Plasmodium falciparum malaria. The present study investigated the efficacy and safety of fixed dose combination (FDC) of arterolane maleate 37.5 mg and piperaquine phosphate (PQP) 187.5 mg dispersible tablets in paediatric patients aged 6 months to 12 years. Male and female patients aged 6 months to 12 years who were confirmed cases of P. falciparum mono-infection with fever or documented history of fever in the previous 24 h were included. The patients were administered FDC of arterolane maleate and PQP as single daily doses for three consecutive days based on their age. The primary efficacy outcome was proportion of patients with polymerase chain reaction (PCR)-corrected adequate clinical and parasitological response (ACPR) on day 28. Safety was analysed based on adverse events (AE), laboratory abnormalities and abnormalities on electrocardiograph. A total of 141 eligible paediatric patients received FDC of arterolane maleate and PQP in a 42-day follow-up study. All the enrolled patients (141) were included in intention to treat (ITT) and safety analyses, and 126 patients were considered in per protocol (PP) population. The PCR-corrected ACPR on day 28 was achieved in all patients (100 %; 95 % CI 97.11-100) included in PP population. The median parasite clearance time (PCT) and fever clearance time (FCT) were 24 h (95 % CI 18.0-24.0) and 10 h (95 % CI 4.0-18.0), respectively. The most frequently reported clinical AE was vomiting. Majority of the AEs were mild to moderate in severity and resolved without sequelae. No patient was discontinued for any QTc (corrected QT interval) prolongation. No deaths or serious AEs were reported during the study. The findings from this study showed that FDC of arterolane maleate and PQP effectively cures P. falciparum malaria and attains acceptable level of cure by day 28 in paediatric patients. The efficacy and

  11. [The goals and tasks of the Roll Back Malaria WHO Cabinet Project].

    Science.gov (United States)

    Binka, F

    2000-01-01

    WHO's Roll Back Malaria Cabinet Project (RBM) has been initiated by WHO Director-General Dr. G. Brundtland in 1998. The World Health Organization, The United Nation's Children's Fund, the United Nation's Development Programme and World Bank have joined forces to fight malaria, which kills more than one million people a year. RBM is being launched at time of growing and investment in malaria, which still remains grossly underfunded. RBM is different from previous efforts to fight malaria. The project is working not only through new tools for controlling the disease but also by involving and strengthening the health services to affected population. This pattern of activities is close to Russian version of malaria eradication programme that had been carried out with the success in the former Soviet Union in the 1950s. RBM seeks to reduce substantially the human suffering and economic losses due one of the most costly diseases. Malaria causes an estimated 300 to 500 million acute cases per year. Malaria is a disease of young and the poor, many of them children who live with no easy access to health service. RBM goal is a significant reduction--ideally halving within ten years--in the global burden of disease associated with malaria. RBM purpose is to create an environment that helps countries develop policies and implement relevant elements of RBM strategy. There are six elements to roll back malaria. They are: early detection of malaria illness; rapid treatment of those who are ill; multiple means for preventing infection; strengthening of health sector and intersectoral activities; a powerful sustained social involvement and movement; focused research for new tools and better implementation. New tools are available to combat malaria. They include among others: rapid diagnostics; new drugs (artesunates) and new means for delivery; impregnated bednets; new means for predicting epidemics (satellite mapping). WHO will be coordinating the RBM project. Endemic countries

  12. Congenital clinical malaria: Incidence, management and outcome ...

    African Journals Online (AJOL)

    ... were the admitted neonates to the emergency paediatric unit and the Special ... no mortality occurred in congenital clinical malaria, however, a diverse pattern of ... mothers of the importance of ante natal clinic visits for prescription of malaria ...

  13. The Malaria Season Is Upon Us

    African Journals Online (AJOL)

    decreased since the last epidemic ten years ago, malaria still remains .... influenza, typhoid, tick bite fever, trypanosomiasis, hepatitis, .... position, at the same ... falciparum malaria: a systematic review and meta-analysis of day 7 lumefantrine.

  14. Complement activation in experimental human malaria infection.

    NARCIS (Netherlands)

    Roestenberg, M.; McCall, M.B.B.; Mollnes, T.E.; Deuren, M. van; Sprong, T.; Klasen, I.S.; Hermsen, C.C.; Sauerwein, R.W.; Ven, A.J.A.M. van der

    2007-01-01

    The objective of this study was to investigate complement activation in uncomplicated, early phases of human malaria. Fifteen healthy volunteers were experimentally infected with Plasmodium falciparum malaria. Parasitemia and complement activation products were assessed. During blood stage parasitem

  15. EU grid computing effort takes on malaria

    CERN Multimedia

    Lawrence, Stacy

    2006-01-01

    Malaria is the world's most common parasitic infection, affecting more thatn 500 million people annually and killing more than 1 million. In order to help combat malaria, CERN has launched a grid computing effort (1 page)

  16. Assessing the association of severe malaria infection and ABO blood groups in northwestern Ethiopia.

    Science.gov (United States)

    Tadesse, Hailu; Tadesse, Kebede

    2013-12-01

    There is lack of adequate information on the association between severe malaria and some human genetic markers like ABO blood types. The study was undertaken to evaluate the association between severe malaria infection and ABO blood types among febrile patients attending Felegeselam Health Center, northwestern Ethiopia. A total of 398 febrile patients were examined for malaria and tested for ABO blood groups in December 2011. The blood samples were collected by finger pricking, stained with Giemsa and slides were examined microscopically. ABO blood group was determined by agglutination test using agglutinating A and B monoclonal anti-sera together with parasite load count. Chi-square and ANOVA tests were used to assess the difference between frequencies and means, respectively. Out of 398 acute febrile patients, 201 (50.5%) were found to be infected with Plasmodium parasites. Of which 194 (48.74%) and 7 (1.76%) belong to Plasmodium falciparum and P. vivax, respectively. The distribution of ABO blood groups was O (46%), A (27.1%), B (23.1%) and AB (3.8%). The percentage of severe malaria with respect to blood group A, B, AB and O was found to be 40, 34.1, 14.3 and 5.1%, respectively. The association of severe malaria with non 'O' blood types was statistically significant (χ2 = 31.246, p <0.01). The present findings indicate that individuals with blood groups A, B and AB are more susceptible for severe malaria infection than blood group O.

  17. The fecal viral flora of wild rodents.

    Directory of Open Access Journals (Sweden)

    Tung G Phan

    2011-09-01

    Full Text Available The frequent interactions of rodents with humans make them a common source of zoonotic infections. To obtain an initial unbiased measure of the viral diversity in the enteric tract of wild rodents we sequenced partially purified, randomly amplified viral RNA and DNA in the feces of 105 wild rodents (mouse, vole, and rat collected in California and Virginia. We identified in decreasing frequency sequences related to the mammalian viruses families Circoviridae, Picobirnaviridae, Picornaviridae, Astroviridae, Parvoviridae, Papillomaviridae, Adenoviridae, and Coronaviridae. Seventeen small circular DNA genomes containing one or two replicase genes distantly related to the Circoviridae representing several potentially new viral families were characterized. In the Picornaviridae family two new candidate genera as well as a close genetic relative of the human pathogen Aichi virus were characterized. Fragments of the first mouse sapelovirus and picobirnaviruses were identified and the first murine astrovirus genome was characterized. A mouse papillomavirus genome and fragments of a novel adenovirus and adenovirus-associated virus were also sequenced. The next largest fraction of the rodent fecal virome was related to insect viruses of the Densoviridae, Iridoviridae, Polydnaviridae, Dicistroviriade, Bromoviridae, and Virgaviridae families followed by plant virus-related sequences in the Nanoviridae, Geminiviridae, Phycodnaviridae, Secoviridae, Partitiviridae, Tymoviridae, Alphaflexiviridae, and Tombusviridae families reflecting the largely insect and plant rodent diet. Phylogenetic analyses of full and partial viral genomes therefore revealed many previously unreported viral species, genera, and families. The close genetic similarities noted between some rodent and human viruses might reflect past zoonoses. This study increases our understanding of the viral diversity in wild rodents and highlights the large number of still uncharacterized viruses in

  18. Orthopox virus infections in Eurasian wild rodents.

    Science.gov (United States)

    Kinnunen, Paula M; Henttonen, Heikki; Hoffmann, Bernd; Kallio, Eva R; Korthase, Christian; Laakkonen, Juha; Niemimaa, Jukka; Palva, Airi; Schlegel, Mathias; Ali, Hanan Sheikh; Suominen, Paula; Ulrich, Rainer G; Vaheri, Antti; Vapalahti, Olli

    2011-08-01

    The genus Orthopoxvirus includes variola (smallpox) virus and zoonotic cowpox virus (CPXV). All orthopoxviruses (OPV) are serologically cross-reactive and cross-protective, and after the cessation of smallpox vaccination, CPXV and other OPV infections represent an emerging threat to human health. In this respect CPXV, with its reservoir in asymptomatically infected wild rodents, is of special importance. In Europe, clinical cowpox has been diagnosed in both humans and animals. The main objective of this study was to elucidate the prevalence of OPV infections in wild rodents in different parts of Eurasia and to compare the performance of three real-time polymerase chain reaction (PCR) methods in detecting OPV DNA in wildlife samples. We investigated 962 wild rodents from Northern Europe (Finland), Central Europe (Germany), and Northern Asia (Siberia, Russia) for the presence of OPV antibodies. According to a CPXV antigen-based immunofluorescence assay, animals from 13 of the 17 locations (76%) showed antibodies. Mean seroprevalence was 33% in Finland (variation between locations 0%-69%), 32% in Germany (0%-43%), and 3.2% (0%-15%) in Siberia. We further screened tissue samples from 513 of the rodents for OPV DNA using up to three real-time PCRs. Three rodents from two German and one Finnish location were OPV DNA positive. The amplicons were 96% to 100% identical to available CPXV sequences. Further, we demonstrated OPV infections as far east as the Baikal region and occurring in hamster and two other rodent species, ones previously unnoticed as possible reservoir hosts. Based on serological and PCR findings, Eurasian wild rodents are frequently but nonpersistently infected with OPVs. Results from three real-time PCR methods were highly concordant. This study extends the geographic range and wildlife species diversity in which OPV (or CPXV) viruses are naturally circulating.

  19. Strategies For Malaria Control In Mangalore City

    OpenAIRE

    Kiran Udaya .N

    1999-01-01

    Research questions: What different strategies should be used to effectively control problem of malaria? Objectives: 1) To study the problem of malaria. 2) To study different strategies for effective control of malaria. Study design: Observational and record based. The problem of malaria was studied for three years from 1996-1998 Participants: Individuals having fever. Setting: Community based in Mangalore City. Study variables: Fever cases, blood slides prepared, slides found positive, agency...

  20. Three different Plasmodium species show similar patterns of clinical tolerance of malaria infection

    Directory of Open Access Journals (Sweden)

    Zimmerman Peter

    2009-07-01

    Full Text Available Abstract Background In areas where malaria endemicity is high, many people harbour blood stage parasites without acute febrile illness, complicating the estimation of disease burden from infection data. For Plasmodium falciparum the density of parasitaemia that can be tolerated is low in the youngest children, but reaches a maximum in the age groups at highest risk of infection. There is little data on the age dependence of tolerance in other species of human malaria. Methods Parasite densities measured in 24,386 presumptive malaria cases at two local health centres in the Wosera area of Papua New Guinea were compared with the distributions of parasite densities recorded in community surveys in the same area. We then analyse the proportions of cases attributable to each of Plasmodium falciparum, P. vivax, and P. malariae as functions of parasite density and age using a latent class model. These attributable fractions are then used to compute the incidence of attributable disease. Results Overall 33.3%, 6.1%, and 0.1% of the presumptive cases were attributable to P. falciparum, P. vivax, and P. malariae respectively. The incidence of attributable disease and parasite density broadly follow similar age patterns. The logarithm of the incidence of acute illness is approximately proportion to the logarithm of the parasite density for all three malaria species, with little age variation in the relationship for P. vivax or P. malariae. P. falciparum shows more age variation in disease incidence at given levels of parasitaemia than the other species. Conclusion The similarities between Plasmodium species in the relationships between parasite density and risk of attributable disease are compatible with the hypothesis that pan-specific mechanisms may regulate tolerance to different human Plasmodia. A straightforward mathematical expression might be used to project disease burden from parasite density distributions assessed in community

  1. Population cycles in small rodents.

    Science.gov (United States)

    Krebs, C J; Gaines, M S; Keller, B L; Myers, J H; Tamarin, R H

    1973-01-05

    We conclude that population fluctuations in Microtus in southern Indiana are produced by a syndrome of changes in birth and death rates similar to that found in other species of voles and lemmings. The mechanisms which cause the changes in birth and death rates are demolished by fencing the population so that no dispersal can occur. Dispersal thus seems critical for population regulation in Microtus. Because most dispersal occurs during the increase phase of the population cycle and there is little dispersal during the decline phase, dispersal is not directly related to population density. Hence the quality of dispersing animals must be important, and we have found one case of increased dispersal tendency by one genotype. The failure of population regulation of Microtus in enclosed areas requires an explanation by any hypothesis attempting to explain population cycles in small rodents. It might be suggested that the fence changed the predation pressure on the enclosed populations. However, the fence was only 2 feet (0.6 meter) high and did not stop the entrance of foxes, weasels, shrews, or avian predators. A striking feature was that the habitat in the enclosures quickly recovered from complete devastation by the start of the spring growing season. Obviously the habitat and food quality were sufficient to support Microtus populations of abnormally high densities, and recovery of the habitat was sufficiently quick that the introduction of new animals to these enclosed areas resulted in another population explosion. Finally, hypotheses of population regulation by social stress must account for the finding that Microtus can exist at densities several times greater than normal without "stress" taking an obvious toll. We hypothesize that the prevention of dispersal changes the quality of the populations in the enclosures in comparison to those outside the fence. Voles forced to remain in an overcrowded fenced population do not suffer high mortality rates and continue

  2. Identification of an AP2-family protein that is critical for malaria liver stage development.

    Directory of Open Access Journals (Sweden)

    Shiroh Iwanaga

    Full Text Available Liver-stage malaria parasites are a promising target for drugs and vaccines against malaria infection. However, little is currently known about gene regulation in this stage. In this study, we used the rodent malaria parasite Plasmodium berghei and showed that an AP2-family transcription factor, designated AP2-L, plays a critical role in the liver-stage development of the parasite. AP2-L-depleted parasites proliferated normally in blood and in mosquitoes. However, the ability of these parasites to infect the liver was approximately 10,000 times lower than that of wild-type parasites. In vitro assays showed that the sporozoites of these parasites invaded hepatocytes normally but that their development stopped in the middle of the liver schizont stage. Expression profiling using transgenic P. berghei showed that fluorescent protein-tagged AP2-L increased rapidly during the liver schizont stage but suddenly disappeared with the formation of the mature liver schizont. DNA microarray analysis showed that the expression of several genes, including those of parasitophorous vacuole membrane proteins, was significantly decreased in the early liver stage of AP2-L-depleted parasites. Investigation of the targets of this transcription factor should greatly promote the exploration of liver-stage antigens and the elucidation of the mechanisms of hepatocyte infection by malaria parasites.

  3. Thermal behaviour of Anopheles stephensi in response to infection with malaria and fungal entomopathogens

    Directory of Open Access Journals (Sweden)

    Read Andrew F

    2009-04-01

    Full Text Available Abstract Background Temperature is a critical determinant of the development of malaria parasites in mosquitoes, and hence the geographic distribution of malaria risk, but little is known about the thermal preferences of Anopheles. A number of other insects modify their thermal behaviour in response to infection. These alterations can be beneficial for the insect or for the infectious agent. Given current interest in developing fungal biopesticides for control of mosquitoes, Anopheles stephensi were examined to test whether mosquitoes showed thermally-mediated behaviour in response to infection with fungal entomopathogens and the rodent malaria, Plasmodium yoelii. Methods Over two experiments, groups of An. stephensi were infected with one of three entomopathogenic fungi, and/or P. yoelii. Infected and uninfected mosquitoes were released on to a thermal gradient (14 – 38°C for "snapshot" assessments of thermal preference during the first five days post-infection. Mosquito survival was monitored for eight days and, where appropriate, oocyst prevalence and intensity was assessed. Results and conclusion Both infected and uninfected An. stephensi showed a non-random distribution on the gradient, indicating some capacity to behaviourally thermoregulate. However, chosen resting temperatures were not altered by any of the infections. There is thus no evidence that thermally-mediated behaviours play a role in determining malaria prevalence or that they will influence the performance of fungal biopesticides against adult Anopheles.

  4. Acute allergic reaction to oral quinine for malarial prevention: A case report

    Directory of Open Access Journals (Sweden)

    Sora Yasri

    2016-01-01

    Full Text Available Quinine is a classical antimalarial drug that is used worldwide. It is also used for pre-exposure of malaria before visiting to the jungle in the endemic area of malaria. In this article, the authors reported a case of acute allergic reaction to oral quinine for malarial prevention.

  5. Viral respiratory tract infections among patients with acute undifferentiated fever in Vietnam

    NARCIS (Netherlands)

    H.L. Phuong; T.T.T. Nga; G.J. van Doornum; J. Groen; T.Q. Binh; P.T. Giao; L.Q. Hung; N.V. Nams; P.A. Kager; P.J. de Vries

    2010-01-01

    To investigate the proportion of viral respiratory tract infections among acute undifferentiated fevers (AUFs) at primary health facilities in southern Vietnam during 2001-2005, patients with AUF not caused by malaria were enrolled at twelve primary health facilities and a clinic for malaria control

  6. Acute allergic reaction to oral quinine for malarial prevention:A case report

    Institute of Scientific and Technical Information of China (English)

    Sora Yasri; Viroj Wiwanitkit

    2016-01-01

    Quinine is a classical antimalarial drug that is used worldwide. It is also used for pre-exposure of malaria before visiting to the jungle in the endemic area of malaria. In this article, the authors reported a case of acute allergic reaction to oral quinine for malarial prevention.

  7. Changing malaria transmission and implications in China towards National Malaria Elimination Programme between 2010 and 2012.

    Directory of Open Access Journals (Sweden)

    Jian-hai Yin

    Full Text Available BACKGROUND: Towards the implementation of national malaria elimination programme in China since 2010, the epidemiology of malaria has changed dramatically, and the lowest malaria burden was achieved yearly. It is time to analyze the changes of malaria situation based on surveillance data from 2010 to 2012 to reconsider the strategies for malaria elimination. METHODS AND PRINCIPAL FINDINGS: Malaria epidemiological data was extracted from the provincial annual reports in China between 2010 and 2012. The trends of the general, autochthonous and imported malaria were analyzed, and epidemic areas were reclassified according to Action Plan of China Malaria Elimination (2010-2020. As a result, there reported 2743 malaria cases with a continued decline in 2012, and around 7% autochthonous malaria cases accounted. Three hundred and fifty-three individual counties from 19 provincial regions had autochthonous malaria between 2010 and 2012, and only one county was reclassified into Type I (local infections detected in 3 consecutive years and the annual incidences ≥ 1/10,000 again. However, the imported malaria cases reported of each year were widespread, and 598 counties in 29 provinces were suffered in 2012. CONCLUSIONS/SIGNIFICANCE: Malaria was reduced significantly from 2010 to 2012 in China, and malaria importation became an increasing challenge. It is necessary to adjust or update the interventions for subsequent malaria elimination planning and resource allocation.

  8. Malaria transmission rates estimated from serological data.

    OpenAIRE

    Burattini, M. N.; Massad, E; Coutinho, F. A.

    1993-01-01

    A mathematical model was used to estimate malaria transmission rates based on serological data. The model is minimally stochastic and assumes an age-dependent force of infection for malaria. The transmission rates estimated were applied to a simple compartmental model in order to mimic the malaria transmission. The model has shown a good retrieving capacity for serological and parasite prevalence data.

  9. Towards malaria elimination - a new thematic series

    Directory of Open Access Journals (Sweden)

    Tanner Marcel

    2010-01-01

    Full Text Available Abstract The launch of a new thematic series of Malaria Journal -- "Towards malaria elimination" -- creates the forum that allows carrying scientific evidence on how to achieve malaria elimination in specific endemic settings and conditions into the circles of scientists, public health specialists, national and global programme managers, funders and decision makers.

  10. Malaria in India: Challenges and opportunities

    Indian Academy of Sciences (India)

    A P Dash; Neena Valecha; A R Anvikar; A Kumar

    2008-11-01

    India contributes about 70% of malaria in the South East Asian Region of WHO. Although annually India reports about two million cases and 1000 deaths attributable to malaria, there is an increasing trend in the proportion of Plasmodium falciparum as the agent. There exists heterogeneity and variability in the risk of malaria transmission between and within the states of the country as many ecotypes/paradigms of malaria have been recognized. The pattern of clinical presentation of severe malaria has also changed and while multi-organ failure is more frequently observed in falciparum malaria, there are reports of vivax malaria presenting with severe manifestations. The high burden populations are ethnic tribes living in the forested pockets of the states like Orissa, Jharkhand, Madhya Pradesh, Chhattisgarh and the North Eastern states which contribute bulk of morbidity and mortality due to malaria in the country. Drug resistance, insecticide resistance, lack of knowledge of actual disease burden along with new paradigms of malaria pose a challenge for malaria control in the country. Considering the existing gaps in reported and estimated morbidity and mortality, need for estimation of true burden of malaria has been stressed. Administrative, financial, technical and operational challenges faced by the national programme have been elucidated. Approaches and priorities that may be helpful in tackling serious issues confronting malaria programme have been outlined.

  11. Gene-therapy for malaria prevention.

    Science.gov (United States)

    Rodrigues, Mauricio M; Soares, Irene S

    2014-11-01

    The limited number of tools for malaria prevention and the inability to eradicate the disease have required large investments in vaccine development, as vaccines have been the only foreseeable type of immunoprophylaxis against malaria. An alternative strategy named vectored immunoprophylaxis (VIP) now would allow genetically transduced host cells to assemble and secrete antibodies that neutralize the infectivity of the malaria parasite and prevent disease.

  12. Immunoinformatics of Placental Malaria Vaccine Development

    DEFF Research Database (Denmark)

    Jessen, Leon Eyrich

    Malaria is an infectious disease caused by a protozoan parasite of the genus Plasmodium, which is transferred by female Anopheles mosquitos. WHO estimates that in 2012 there were 207 million cases of malaria, of which 627,000 were fatal. People living in malaria-endemic areas, gradually acquire...

  13. Serum transferrin receptor concentration indicates increased erythropoiesis in Kenyan children with asymptomatic malaria.

    Science.gov (United States)

    Verhoef, H; West, C E; Ndeto, P; Burema, J; Beguin, Y; Kok, F J

    2001-12-01

    Serum transferrin receptor concentrations indicate both erythropoietic activity and the deficit of functional iron in the erythron. In contrast with serum ferritin concentrations, serum transferrin receptor concentrations are not or are only marginally influenced by the inflammatory response to infection. We assessed iron status and examined the relation between serum transferrin receptor concentrations and malaria in children aged 2-36 mo who were asymptomatic for malaria. This was a community-based cluster survey (n = 318). Prevalences of malaria, anemia (hemoglobin concentration serum ferritin concentration Malaria was associated with lower mean hemoglobin concentrations (92.7 compared with 104.1 g/L; P = 0.0001) and higher geometric mean serum concentrations of transferrin receptor (11.4 compared with 7.8 mg/L; P = 0.005), ferritin (21.6 compared with 11.9 microg/L; P = 0.05), and C-reactive protein (12.5 compared with 6.8 mg/L; P = 0.004). There was no evidence for an association between serum concentrations of C-reactive protein and transferrin receptor. Children with malaria had higher serum transferrin receptor concentrations than expected for the degree of anemia, even after adjustment for inflammation indicated by serum C-reactive protein concentration quartiles (P = 0.02). Our findings are consistent with the notion that malaria-induced hemolysis is accompanied by increased erythropoiesis. Serum transferrin receptor concentration is not useful for detecting iron deficiency in individuals with malaria. Individuals with high concentrations of serum C-reactive protein or similar acute phase reactants should be excluded from analysis if serum ferritin concentrations malaria-endemic areas.

  14. Averting a malaria disaster: will insecticide resistance derail malaria control?

    Science.gov (United States)

    Hemingway, Janet; Ranson, Hilary; Magill, Alan; Kolaczinski, Jan; Fornadel, Christen; Gimnig, John; Coetzee, Maureen; Simard, Frederic; Roch, Dabiré K; Hinzoumbe, Clément Kerah; Pickett, John; Schellenberg, David; Gething, Peter; Hoppé, Mark; Hamon, Nicholas

    2016-04-23

    World Malaria Day 2015 highlighted the progress made in the development of new methods of prevention (vaccines and insecticides) and treatment (single dose drugs) of the disease. However, increasing drug and insecticide resistance threatens the successes made with existing methods. Insecticide resistance has decreased the efficacy of the most commonly used insecticide class of pyrethroids. This decreased efficacy has increased mosquito survival, which is a prelude to rising incidence of malaria and fatalities. Despite intensive research efforts, new insecticides will not reach the market for at least 5 years. Elimination of malaria is not possible without effective mosquito control. Therefore, to combat the threat of resistance, key stakeholders need to rapidly embrace a multifaceted approach including a reduction in the cost of bringing new resistance management methods to market and the streamlining of associated development, policy, and implementation pathways to counter this looming public health catastrophe.

  15. The association between malaria and iron status or supplementation in pregnancy: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Laura Sangaré

    Full Text Available INTRODUCTION: Malaria prevention and iron supplementation are associated with improved maternal and infant outcomes. However, evidence from studies in children suggests iron may adversely modify the risk of malaria. We reviewed the evidence in pregnancy of the association between malaria and markers of iron status, iron supplementation or parenteral treatment. METHODS AND FINDINGS: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Global Health Library, and the Malaria in Pregnancy library to identify studies that investigated the association between iron status, iron treatment or supplementation during pregnancy and malaria. Thirty one studies contributed to the analysis; 3 experimental and 28 observational studies. Iron supplementation was not associated with an increased risk of P. falciparum malaria during pregnancy or delivery in Africa (summary Relative Risk = 0.89, 95% Confidence Interval (CI 0.66-1.20, I(2 = 78.8%, 5 studies. One study in Asia reported an increased risk of P. vivax within 30 days of iron supplementation (e.g. adjusted Hazard Ratio = 1.75, 95% CI 1.14-2.70 for 1-15 days, but not after 60 days. Iron deficiency (based on ferritin and C-reactive protein was associated with lower odds for malaria infection (summary Odds Ratio = 0.35, 0.24-0.51, I(2 = 59.2%, 5 studies. With the exception of the acute phase protein ferritin, biomarkers of iron deficiency were generally not associated with malaria infection. CONCLUSIONS: Iron supplementation was associated with a temporal increase in P vivax, but not with an increased risk of P. falciparum; however, data are insufficient to rule out the potential for an increased risk of P. falciparum. Iron deficiency was associated with a decreased malaria risk in pregnancy only when measured with ferritin. Until there is more evidence, it is prudent to provide iron in combination with malaria prevention during pregnancy.

  16. Malaria Surveillance - United States, 2014.

    Science.gov (United States)

    Mace, Kimberly E; Arguin, Paul M

    2017-05-26

    Malaria in humans is caused by intraerythrocytic protozoa of the genus Plasmodium. These parasites are transmitted by the bite of an infective female Anopheles mosquito. The majority of malaria infections in the United States occur among persons who have traveled to regions with ongoing malaria transmission. However, malaria is occasionally acquired by persons who have not traveled out of the country through exposure to infected blood products, congenital transmission, laboratory exposure, or local mosquitoborne transmission. Malaria surveillance in the United States is conducted to identify episodes of local transmission and to guide prevention recommendations for travelers. This report summarizes cases in persons with onset of illness in 2014 and trends during previous years. Malaria cases diagnosed by blood film, polymerase chain reaction, or rapid diagnostic tests are reported to local and state health departments by health care providers or laboratory staff. Case investigations are conducted by local and state health departments, and reports are transmitted to CDC through the National Malaria Surveillance System, National Notifiable Diseases Surveillance System, or direct CDC consultations. CDC conducts antimalarial drug resistance marker testing on blood samples submitted by health care providers or local or state health departments. Data from these reporting systems serve as the basis for this report. CDC received reports of 1,724 confirmed malaria cases, including one congenital case and two cryptic cases, with onset of symptoms in 2014 among persons in the United States. The number of confirmed cases in 2014 is consistent with the number of confirmed cases reported in 2013 (n = 1,741; this number has been updated from a previous publication to account for delayed reporting for persons with symptom onset occurring in late 2013). Plasmodium falciparum, P. vivax, P. ovale, and P. malariae were identified in 66.1%, 13.3%, 5.2%, and 2.7% of cases, respectively

  17. Nitric oxide bioavailability in malaria.

    Science.gov (United States)

    Sobolewski, Peter; Gramaglia, Irene; Frangos, John; Intaglietta, Marcos; van der Heyde, Henri C

    2005-09-01

    Rational development of adjunct or anti-disease therapy for severe Plasmodium falciparum malaria requires cellular and molecular definition of malarial pathogenesis. Nitric oxide (NO) is a potential target for such therapy but its role during malaria is controversial. It has been proposed that NO is produced at high levels to kill Plasmodium parasites, although the unfortunate consequence of elevated NO levels might be impaired neuronal signaling, oxidant damage and red blood cell damage that leads to anemia. In this case, inhibitors of NO production or NO scavengers might be an effective adjunct therapy. However, increasing amounts of evidence support the alternate hypothesis that NO production is limited during malaria. Furthermore, the well-documented NO scavenging by cell-free plasma hemoglobin and superoxide, the levels of which are elevated during malaria, has not been considered. Low NO bioavailability in the vasculature during malaria might contribute to pathologic activation of the immune system, the endothelium and the coagulation system: factors required for malarial pathogenesis. Therefore, restoring NO bioavailability might represent an effective anti-disease therapy.

  18. [Malaria and intestinal protozoa].

    Science.gov (United States)

    Rojo-Marcos, Gerardo; Cuadros-González, Juan

    2016-03-01

    Malaria is life threatening and requires urgent diagnosis and treatment. Incidence and mortality are being reduced in endemic areas. Clinical features are unspecific so in imported cases it is vital the history of staying in a malarious area. The first line treatments for Plasmodium falciparum are artemisinin combination therapies, chloroquine in most non-falciparum and intravenous artesunate if any severity criteria. Human infections with intestinal protozoa are distributed worldwide with a high global morbid-mortality. They cause diarrhea and sometimes invasive disease, although most are asymptomatic. In our environment populations at higher risk are children, including adopted abroad, immune-suppressed, travelers, immigrants, people in contact with animals or who engage in oral-anal sex. Diagnostic microscopic examination has low sensitivity improving with antigen detection or molecular methods. Antiparasitic resistances are emerging lately. Copyright © 2016 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  19. Endoparasites of Wild Rodents in Southeastern Iran

    Directory of Open Access Journals (Sweden)

    Mehdi Nateghpour

    2015-10-01

    Full Text Available Background: This study was aimed to collect wild rodents for endoparasites determination in some parts of Sistan and Baluchistan Province, southeastern Iran nearby Pakistan and Afghanistan countries.Methods: A total of 100 wild rodents were captured alive with cage traps. Various samples were collected from blood and feces, also impression smear prepared from different organs. The samples were prepared by formalin-ether or stained with Giemsa, after that were examined under microscope.Results: All the caught rodents (47 Tatera indica, 44 Meriones hurriana, 5 Gerbilus nanus and 4 Meriones libycus were studied for endoparasites emphasizing to their zoonotic aspects. Endoparasites including Spirurida,Hymenolepis diminuta, Hymenolepis nana feraterna, Trichuris trichiura, Skerjabino taenia, Trichostrongylus spp, Entamoeba muris, Chilomastix mesnili and Leishmania spp were parasitologically identified.Conclusion: Among 9 genera or species of the identified parasites at least 5 of them have zoonotic and public health importance.

  20. [Application of genetic diversity in the researches on rodents].

    Science.gov (United States)

    Liu, Zhu; Yang, Chun-Wen; Xu, Yan-Chun; Jin, Zhi-Min; Ma, Jian-Zhang

    2014-02-01

    Genetic diversity is the base of the species diversity and ecosystem diversity, and also the foundation for biological evolution and species differentiation. Furthermore, genetic diversity is important evidence for evaluation of biological resources of nature. The genetic diversity data from a wide variety of rodents have many complex applications. We summarized the application of rodent prevention, the origin and differentiation including evolutionary history of rodents, the potential adaptation of rodents, the dynamics of population and regulatory mechanisms, and the conservation biology of rodents. Researches in the future should focus on the systematic study on the relationships between population dynamics and genetic diversity, and long-term monitoring of genetic diversity of rodents.

  1. A new clinical variant of the post-malaria neurological syndrome.

    Science.gov (United States)

    Pace, Adrian A; Edwards, Simon; Weatherby, Stuart

    2013-11-15

    Post-malaria neurological syndrome (PMNS) is an uncommon, monophasic illness that occurs within two months following recovery from Plasmodium falciparum (Pf) malaria. Clinical manifestations of PMNS are variable, but published cases uniformly feature neurological and/or psychiatric symptoms without long tract signs. We describe a case of severe brainstem and spinal cord inflammation with paraplegia and sphincter involvement in a 48 year old woman following recovery from a Pf malarial illness. We propose that this case represents a previously unreported form of PMNS, which has features that distinguish it from acute disseminated encephalomyelitis, and that the recognised clinical spectrum of PMNS should be extended to include brainstem and spinal cord inflammation.

  2. Cutaneous findings in five cases of malaria

    Directory of Open Access Journals (Sweden)

    Jignesh B Vaishnani

    2011-01-01

    Full Text Available Malaria is an infectious disease caused by protozoa of the genus Plasmodium. Cutaneous lesions in malaria are rarely reported and include urticaria, angioedema, petechiae, purpura, and disseminated intravascular coagulation (DIC. Here, five malaria cases associated with cutaneous lesions have been described. Out of the five cases of malaria, two were associated with urticaria and angioedema, one case was associated with urticaria, and other two were associated with reticulated blotchy erythema with petechiae. Most of the cutaneous lesions in malaria were nonspecific and reflected the different immunopathological mechanism in malarial infection.

  3. Malaria vaccine: a step toward elimination.

    Science.gov (United States)

    Jindal, Harashish; Bhatt, Bhumika; Malik, Jagbir S; Sk, Shashikantha; Mehta, Bharti

    2014-01-01

    Malaria has long been recognized as a public health problem. At the community level, vector control, and antimalarial medicines are the main means for reducing incidence, morbidity, and mortality of malaria. A vaccine not only would bring streamlining in the prevention of morbidity and mortality from malaria but also would be more accessible if integrated with Expanded Programme of Immunization (EPI). Globally, an estimated 3.4 billion people are at risk of malaria. Most cases (80%) and deaths (90%) occurred in Africa, and most deaths (77%) are in children under 5 years of age. An effective vaccine has long been envisaged as a valuable addition to the available tools for malaria control. Although research toward the development of malaria vaccines has been pursued since the 1960s, there are no licensed malaria vaccines. The RTS,S/AS01 vaccine, which targets P. falciparum, has reached phase 3 clinical trials and results are promising. Malaria Vaccine Technology Road Map 2013 has envisaged the world aiming for a licensed vaccine by 2030 that would reduce malaria cases by 75% and be capable of eliminating malaria. It will not only fill the gaps of today's interventions but also be a cost-effective method of decreasing morbidity and mortality from malaria.

  4. CLINICAL ASPECTS OF UNCOMPLICATED AND SEVERE MALARIA

    Directory of Open Access Journals (Sweden)

    Alessandro Bartoloni

    2012-05-01

    Full Text Available The first symptoms of malaria, common to all the different malaria species, are nonspecific and mimic a flu-like syndrome. Although fever represents the cardinal feature, clinical findings in malaria are extremely diverse and may range in severity from mild headache to serious complications leading to death, particularly in falciparum malaria. As the progression to these complications can be rapid, any malaria patient must be assessed and treated rapidly, and frequent observations are needed to look for early signs of systemic complications. In fact, severe malaria is a life threatening but treatable disease.  The protean and nonspecific clinical findings occurring in malaria (fever, malaise, headache, myalgias, jaundice and sometimes gastrointestinal symptoms of nausea, vomiting and diarrhoea may lead physicians who see malaria infrequently to a wrong diagnosis, such as influenza (particularly during the seasonal epidemic flu, dengue, gastroenteritis, typhoid fever, viral hepatitis, encephalitis. Physicians should be aware that malaria is not a clinical diagnosis but must be diagnosed, or excluded, by performing microscopic examination of blood films. Prompt diagnosis and appropriate treatment are then crucial to prevent morbidity and fatal outcomes. Although Plasmodium falciparum malaria is the major cause of severe malaria and death, increasing evidence has recently emerged that Plasmodium vivax and Plasmodium knowlesi can also be severe and even fatal.

  5. The Effect of Reduced Glutathione on Oxidative Stress in the Rodent Model of Cisplatin Induced Acute Kidney Injury%还原型谷胱甘肽对顺铂致大鼠急性肾损伤氧化应激的影响

    Institute of Scientific and Technical Information of China (English)

    孟晓燕; 黄向阳; 王英; 刘倩

    2013-01-01

    Objective:To observe the effect of reduced glutathione on oxidative stress in the rodent model of cisplatin induced acute kidney injury(AKI). Method:66 male wistar rats were randomly assigned to three groups.The rats of CP group(n=30) were injected once intraperitoneal with cisplatin at 10 mg/kg, the rats of CN group were injected intraperitoneal with same volume of normal saline vehicle,the GI group were injected intraperitoneal with reduced glutathione at 800 mg/kg before cisplatin injection.Rats were euthanized at 12,24,48,96 and 144 hours(n=6 in the CP group at each time point and n=6 in the GI group at each time point).The blood and kidney samples were analyzed at each time point.Result:A significant increase in serum creatinine was noted by 48 hours in the CP group versus CN group,peak levels of serum creatinine were seen on 144 hours(P<0.05).The levels of MDA in renal tissues were significantly higher by 48 hours in the CP group than in the CN group(P<0.05).The levels of SOD in renal tissues were significantly lower by 48 hours in the CP group than in the CN group(P<0.05).Compared with CP group,the levels of SOD in renal tissues increase significantly in GI 48 hours group,while the levels of MDA in renal tissues decreased significantly in GI 48 hours group.Conclusion:Reduced glutathione can attenuate the cisplatin induced AKI in rodent model,which may be associated with anti-oxidative stress effect.%目的::研究还原型谷胱甘肽对顺铂致大鼠急性肾损伤氧化应激的影响。方法:66只健康雄性Wistar大鼠为研究对象,随机数字法分为盐水对照组(CN组),顺铂模型组(CP组)及还原型谷胱甘肽干预组(GI组),CP组为腹腔单次注射顺铂10 mg/kg,据给药后各时间点不同分为CP 12 h组、CP 24 h组、CP 48 h组、CP 96 h组、CP 144 h组;GI组为应用顺铂前腹腔注射还原型谷胱甘肽800 mg/kg,同样据给药时间不同分为GI 12 h组、GI 24 h组、GI 48 h组、GI 96 h组、GI 144

  6. Prolonged incubation period of imported P. vivax malaria in London.

    Science.gov (United States)

    Warwick, R; Swimer, G J; Britt, R P

    1980-05-01

    Between January 1976 and July 1979, 453 cases of malaria were seen at Hillingdon Hospital. The majority of cases were Plasmodium vivax infections in Asians from the Punjab in Northern India-either new immigrants or United Kingdom resident Asians returning from holidays. Twenty-four cases were contracted in Africa or the Middle East. Figures are presented showing a considerable increase in cases during the period of study. In P. vivax infections the time interval between arrival and development of the acute illness was significantly greater for those subjects entering the United Kingdom in autumn or winter.

  7. Anopheles gambiae immune responses to human and rodent Plasmodium parasite species.

    Directory of Open Access Journals (Sweden)

    Yuemei Dong

    2006-06-01

    Full Text Available Transmission of malaria is dependent on the successful completion of the Plasmodium lifecycle in the Anopheles vector. Major obstacles are encountered in the midgut tissue, where most parasites are killed by the mosquito's immune system. In the present study, DNA microarray analyses have been used to compare Anopheles gambiae responses to invasion of the midgut epithelium by the ookinete stage of the human pathogen Plasmodium falciparum and the rodent experimental model pathogen P. berghei. Invasion by P. berghei had a more profound impact on the mosquito transcriptome, including a variety of functional gene classes, while P. falciparum elicited a broader immune response at the gene transcript level. Ingestion of human malaria-infected blood lacking invasive ookinetes also induced a variety of immune genes, including several anti-Plasmodium factors. Twelve selected genes were assessed for effect on infection with both parasite species and bacteria using RNAi gene silencing assays, and seven of these genes were found to influence mosquito resistance to both parasite species. An MD2-like receptor, AgMDL1, and an immunolectin, FBN39, showed specificity in regulating only resistance to P. falciparum, while the antimicrobial peptide gambicin and a novel putative short secreted peptide, IRSP5, were more specific for defense against the rodent parasite P. berghei. While all the genes that affected Plasmodium development also influenced mosquito resistance to bacterial infection, four of the antimicrobial genes had no effect on Plasmodium development. Our study shows that the impact of P. falciparum and P. berghei infection on A. gambiae biology at the gene transcript level is quite diverse, and the defense against the two Plasmodium species is mediated by antimicrobial factors with both universal and Plasmodium-species specific activities. Furthermore, our data indicate that the mosquito is capable of sensing infected blood constituents in the absence

  8. The Impact of Nanochloroquine on Restoration of Hepatic and Splenic Mitochondrial Damage against Rodent Malaria

    Directory of Open Access Journals (Sweden)

    Satyajit Tripathy

    2013-01-01

    Full Text Available The applications of nanotechnology to pharmacology are the potential appliance of biodegradable polymers and convection-enhanced drug delivery in the diagnostics and treatment of diseases. Chitosan is a natural polysaccharide that has attracted significant scientific interest during the last two decades. The present study was to evaluate the possible effects of chitosan tripolyphosphate conjugated nanochloroquine against Plasmodium berghei infection on select makers of oxidative damage and antioxidant status in mitochondria of liver and spleen. P. berghei infection was developed in Swiss mice by intraperitoneal injection of 200 µL of infected blood. Parasite-infected mice were treated with chloroquine and nanoconjugated chloroquine. Superoxide radical generation, nitrate level, and oxidized glutathione were increased significantly (P<0.05 in the mitochondria of infected group as compared to control group, and reduced glutathione level, activity of SOD, GPx, GR, and GST, and mitochondrial transmembrane potential were decreased significantly (P<0.05, which were increased or decreased significantly (P<0.05 near to normal in nanoconjugated chloroquine treated group than chloroquine treated group. So, the findings may suggest the advantageous role of nanoconjugated chloroquine against the P. berghei induced oxidative damage in hepatic and splenic mitochondria.

  9. Rodent malaria in rats exacerbated by milk protein, attenuated by low-protein vegetable diet

    NARCIS (Netherlands)

    Doorne, C.W. van; Eling, W.M.C.; Luyken, R.

    1998-01-01

    Young male Wistar rats were fed a purified, vegetable, low-protein diet containing 6% protein from maize gluten and 2% from soy protein isolate, or comparable diets in which maize gluten was replaced partly or completely by the equivalent amount of a milk protein concentrate. Diets with adequate

  10. Rodent malaria in rats exacerbated by milk protein, attenuated by low-protein vegetable diet

    NARCIS (Netherlands)

    Doorne, C.W. van; Eling, W.M.C.; Luyken, R.

    1998-01-01

    Young male Wistar rats were fed a purified, vegetable, low-protein diet containing 6% protein from maize gluten and 2% from soy protein isolate, or comparable diets in which maize gluten was replaced partly or completely by the equivalent amount of a milk protein concentrate. Diets with adequate pro

  11. Comparative study of chloroquine and quinine on malaria rodents and their effects on the mouse testis

    Institute of Scientific and Technical Information of China (English)

    Esmail Abolghasemi; Seyed Hassan Moosa-Kazemi; Maryam Davoudi; Ahmad Reisi; Mohammad Taghi Satvat

    2012-01-01

    Objective: To evaluate the effects of quinine and chloroquine against male mice infected withPlasmodium berghei and their adverse effects on the mice testes. Methods: In this study, 48 adult male mice, (20-25 g), aged 8 to 12 weeks were divided into four groups. This study was carried out from December 2009 until May 2010 in the School of Public Health, Tehran University of Medical Sciences. Results: The results showed that 58.33% of mice treated with chloroquine were completely recovered. Parasitemia was 4% on day 8 when compared to that on day 0, whereas it was 9% on day 9. There was no orchitis found in this group. The mortality of mice after exposing to quinine on day 5 was 8.3%, whereas from day 10 to day 14 it was 91.7%. We found 75% orchitis occurred in quinine treated group. There was a significant difference between quinine and chloroquine effects on the parasite and also mice testes (P<0.05). Conclusions: In this study, It can be concluded that male mice have full resistance to the quinine. Quinine does not only make male mice recover completely, but also cause inflammation on mice testicles tissue.

  12. An efficient strategy for gene targeting and phenotypic assessment in the Plasmodium yoelii rodent malaria model.

    Science.gov (United States)

    Mikolajczak, Sebastian A; Aly, Ahmed S I; Dumpit, Ronald F; Vaughan, Ashley M; Kappe, Stefan H I

    2008-04-01

    In this report, we describe a cloning procedure for gene replacement by double homologous recombination in Plasmodium yoelii, which requires only one digestion and ligation step. This significantly shortens the time required to complete the production of the targeting vector. Furthermore, for more efficient phenotypic evaluation of the gene knockout parasites, we have also introduced a fluorescent protein cassette into the targeting vector. This allows for a more rapid assessment of parasite growth in all of its developmental stages. In addition, the introduction of the fluorescent marker via the replacement strategy confers the stable integration of the marker.

  13. Filariasis attenuates anemia and proinflammatory responses associated with clinical malaria: a matched prospective study in children and young adults.

    Directory of Open Access Journals (Sweden)

    Housseini Dolo

    Full Text Available BACKGROUND: Wuchereria bancrofti (Wb and Mansonella perstans (Mp are blood-borne filarial parasites that are endemic in many countries of Africa, including Mali. The geographic distribution of Wb and Mp overlaps considerably with that of malaria, and coinfection is common. Although chronic filarial infection has been shown to alter immune responses to malaria parasites, its effect on clinical and immunologic responses in acute malaria is unknown. METHODOLOGY/PRINCIPAL FINDINGS: To address this question, 31 filaria-positive (FIL+ and 31 filaria-negative (FIL- children and young adults, matched for age, gender and hemoglobin type, were followed prospectively through a malaria transmission season. Filarial infection was defined by the presence of Wb or Mp microfilariae on calibrated thick smears performed between 10 pm and 2 am and/or by the presence of circulating filarial antigen in serum. Clinical malaria was defined as axillary temperature ≥37.5°C or another symptom or sign compatible with malaria infection plus the presence of asexual malaria parasites on a thick blood smear. Although the incidence of clinical malaria, time to first episode, clinical signs and symptoms, and malaria parasitemia were comparable between the two groups, geometric mean hemoglobin levels were significantly decreased in FIL- subjects at the height of the transmission season compared to FIL+ subjects (11.4 g/dL vs. 12.5 g/dL, p<0.01. Plasma levels of IL-1ra, IP-10 and IL-8 were significantly decreased in FIL+ subjects at the time of presentation with clinical malaria (99, 2145 and 49 pg/ml, respectively as compared to 474, 5522 and 247 pg/ml in FIL- subjects. CONCLUSIONS/SIGNIFICANCE: These data suggest that pre-existent filarial infection attenuates immune responses associated with severe malaria and protects against anemia, but has little effect on susceptibility to or severity of acute malaria infection. The apparent protective effect of filarial infection

  14. Ongoing challenges in the management of malaria.

    Science.gov (United States)

    Kokwaro, Gilbert

    2009-10-12

    This article gives an overview of some of the ongoing challenges that are faced in the prevention, diagnosis and treatment of malaria. Malaria causes approximately 881,000 deaths every year, with nine out of ten deaths occurring in sub-Saharan Africa. In addition to the human burden of malaria, the economic burden is vast. It is thought to cost African countries more than US$12 billion every year in direct losses. However, great progress in malaria control has been made in some highly endemic countries. Vector control is assuming a new importance with the significant reductions in malaria burden achieved using combined malaria control interventions in countries such as Zanzibar, Zambia and Rwanda. The proportion of patients treated for malaria who have a confirmed diagnosis is low in Africa compared with other regions of the world, with the result that anti-malarials could be used to treat patients without malaria, especially in areas where progress has been made in reducing the malaria burden and malaria epidemiology is changing. Inappropriate administration of anti-malarials could contribute to the spread of resistance and incurs unnecessary costs. Parasite resistance to almost all commonly used anti-malarials has been observed in the most lethal parasite species, Plasmodium falciparum. This has presented a major barrier to successful disease management in malaria-endemic areas. ACT (artemisinin-based combination therapy) has made a significant contribution to malaria control and to reducing disease transmission through reducing gametocyte carriage. Administering ACT to infants and small children can be difficult and time consuming. Specially formulating anti-malarials for this vulnerable population is vital to ease administration and help ensure that an accurate dose is received. Education of healthworkers and communities about malaria prevention, diagnosis and treatment is a vital component of effective case management, especially as diagnostic policies change

  15. An open source business model for malaria.

    Science.gov (United States)

    Årdal, Christine; Røttingen, John-Arne

    2015-01-01

    Greater investment is required in developing new drugs and vaccines against malaria in order to eradicate malaria. These precious funds must be carefully managed to achieve the greatest impact. We evaluate existing efforts to discover and develop new drugs and vaccines for malaria to determine how best malaria R&D can benefit from an enhanced open source approach and how such a business model may operate. We assess research articles, patents, clinical trials and conducted a smaller survey among malaria researchers. Our results demonstrate that the public and philanthropic sectors are financing and performing the majority of malaria drug/vaccine discovery and development, but are then restricting access through patents, 'closed' publications and hidden away physical specimens. This makes little sense since it is also the public and philanthropic sector that purchases the drugs and vaccines. We recommend that a more "open source" approach is taken by making the entire value chain more efficient through greater transparency which may lead to more extensive collaborations. This can, for example, be achieved by empowering an existing organization like the Medicines for Malaria Venture (MMV) to act as a clearing house for malaria-related data. The malaria researchers that we surveyed indicated that they would utilize such registry data to increase collaboration. Finally, we question the utility of publicly or philanthropically funded patents for malaria medicines, where little to no profits are available. Malaria R&D benefits from a publicly and philanthropically funded architecture, which starts with academic research institutions, product development partnerships, commercialization assistance through UNITAID and finally procurement through mechanisms like The Global Fund to Fight AIDS, Tuberculosis and Malaria and the U.S.' President's Malaria Initiative. We believe that a fresh look should be taken at the cost/benefit of patents particularly related to new malaria

  16. An open source business model for malaria.

    Directory of Open Access Journals (Sweden)

    Christine Årdal

    Full Text Available Greater investment is required in developing new drugs and vaccines against malaria in order to eradicate malaria. These precious funds must be carefully managed to achieve the greatest impact. We evaluate existing efforts to discover and develop new drugs and vaccines for malaria to determine how best malaria R&D can benefit from an enhanced open source approach and how such a business model may operate. We assess research articles, patents, clinical trials and conducted a smaller survey among malaria researchers. Our results demonstrate that the public and philanthropic sectors are financing and performing the majority of malaria drug/vaccine discovery and development, but are then restricting access through patents, 'closed' publications and hidden away physical specimens. This makes little sense since it is also the public and philanthropic sector that purchases the drugs and vaccines. We recommend that a more "open source" approach is taken by making the entire value chain more efficient through greater transparency which may lead to more extensive collaborations. This can, for example, be achieved by empowering an existing organization like the Medicines for Malaria Venture (MMV to act as a clearing house for malaria-related data. The malaria researchers that we surveyed indicated that they would utilize such registry data to increase collaboration. Finally, we question the utility of publicly or philanthropically funded patents for malaria medicines, where little to no profits are available. Malaria R&D benefits from a publicly and philanthropically funded architecture, which starts with academic research institutions, product development partnerships, commercialization assistance through UNITAID and finally procurement through mechanisms like The Global Fund to Fight AIDS, Tuberculosis and Malaria and the U.S.' President's Malaria Initiative. We believe that a fresh look should be taken at the cost/benefit of patents particularly related

  17. Malaria successes and challenges in Asia.

    Science.gov (United States)

    Bhatia, Rajesh; Rastogi, Rakesh Mani; Ortega, Leonard

    2013-12-01

    Asia ranks second to Africa in terms of malaria burden. In 19 countries of Asia, malaria is endemic and 2.31 billion people or 62% of the total population in these countries are at risk of malaria. In 2010, WHO estimated around 34.8 million cases and 45,600 deaths due to malaria in Asia. In 2011, 2.7 million cases and > 2000 deaths were reported. India, Indonesia, Myanmar and Pakistan are responsible for >85% of the reported cases (confirmed) and deaths in Asia. In last 10 yr, due to availability of donor's fund specially from Global fund, significant progress has been made by the countries in Asia in scaling-up malaria control interventions which were instrumental in reducing malaria morbidity and mortality significantly. There is a large heterogeneity in malaria epidemiology in Asia. As a result, the success in malaria control/elimination is also diverse. As compared to the data of the year 2000, out of 19 malaria endemic countries, 12 countries were able to reduce malaria incidence (microscopically confirmed cases only) by 75%. Two countries, namely Bangladesh and Malaysia are projected to reach 75% reduction by 2015 while India is projected to reach 50-75% only by 2015. The trend could not be assessed in four countries, namely Indonesia, Myanmar, Pakistan and Timor-Leste due to insufficient consistent data. Numerous key challenges need to be addressed to sustain the gains and eliminate malaria in most parts of Asia. Some of these are to control the spread of resistance in Plasmodium falciparum to artemisinin, control of outdoor transmission, control of vivax malaria and ensuring universal coverage of key interventions. Asia has the potential to influence the malaria epidemiology all over the world as well as to support the global efforts in controlling and eliminating malaria through production of quality-assured ACTs, RDTs and long-lasting insecticidal nets.

  18. Antibody responses to Rhoptry-Associated Protein-1 (RAP-1) of Plasmodium falciparum parasites in humans from areas of different malaria endemicity

    DEFF Research Database (Denmark)

    Jakobsen, P H; Kurtzhals, J A; Riley, E M

    1997-01-01

    Plasma IgM and IgG antibody reactivities against the recombinant Plasmodium falciparum protein, Rhoptry Associated Protein-1 (rRAP-1) were measured by ELISA in individuals from Sudan, Indonesia, Kenya and The Gambia living in areas of different malaria endemicity. IgG and IgM reactivities to rRAP-1...... increased with malaria endemicity. IgG reactivities were associated with spleen rates in Indonesia with high malaria endemicity while IgM reactivities were associated with spleen rates in Kenya with low malaria endemicity. IgG and IgM reactivities to rRAP-1 increased during acute episodes of P. falciparum...... malaria in Sudanese adults and IgG reactivities remained high one month after treatment in all adults tested. Antibody reactivities to rRAP-1 in Gambian children in the dry season were higher in children with parasitaemia than in children without detectable parasitaemia. Antibody reactivities were...

  19. PKC-mediated potentiation of morphine analgesia by St. John's Wort in rodents and humans.

    Science.gov (United States)

    Galeotti, Nicoletta; Farzad, Mersedeh; Bianchi, Enrica; Ghelardini, Carla

    2014-01-01

    Our purpose was to combine the use of morphine with clinically available inhibitors of protein kinase C (PKC), finally potentiating morphine analgesia in humans. Thermal tests were performed in rodents and humans previously administered with acute or chronic morphine combined or not with increasing doses of the PKC-blocker St. John's Wort (SJW) or its main component hypericin. Phosphorylation of the γ subunit of PKC enzyme was assayed by western blotting in the periaqueductal grey matter (PAG) from rodents co-administered with morphine and hypericin and was prevented in rodent PAG by SJW or hypericin co-administration with morphine, inducing a potentiation of morphine analgesia in thermal pain. The score of pain assessment in healthy volunteers were decreased by 40% when morphine was co-administered with SJW at a dose largely below those used to obtain an antidepressant or analgesic effect in both rodents and humans. The SJW/hypericin potentiating effect lasted in time and preserved morphine analgesia in tolerant mice. Our findings indicate that, in clinical practice, SJW could reduce the dose of morphine obtaining the same analgesic effect. Therefore, SJW and one of its main components, hypericin, appear ideal to potentiate morphine-induced analgesia.

  20. Object Recognition Memory and the Rodent Hippocampus

    Science.gov (United States)

    Broadbent, Nicola J.; Gaskin, Stephane; Squire, Larry R.; Clark, Robert E.

    2010-01-01

    In rodents, the novel object recognition task (NOR) has become a benchmark task for assessing recognition memory. Yet, despite its widespread use, a consensus has not developed about which brain structures are important for task performance. We assessed both the anterograde and retrograde effects of hippocampal lesions on performance in the NOR…

  1. Neurogenic inflammation in human and rodent skin

    DEFF Research Database (Denmark)

    Schmelz, M; Petersen, Lars Jelstrup

    2001-01-01

    The combination of vasodilation and protein extravasation following activation of nociceptors has been termed "neurogenic inflammation." In contrast to rodents, no neurogenic protein extravasation can be elicited in healthy human skin. Dermal microdialysis has considerably increased our knowledge...... about neurogenic inflammation in human skin, including the involvement of mast cells....

  2. Estimating body mass of fossil rodents

    NARCIS (Netherlands)

    Freudenthal, M.; Martín-Suárez, E.

    2013-01-01

    Reconstructing the body mass of a fossil animal is an essential step toward understanding its palaeoecological role. Length × width (L×W) of the first lower molar (m1) is frequently used as a proxy for body mass in fossil mammals. However, among rodents, Muroidea have no premolar and an elongated m1

  3. Utility of health facility-based malaria data for malaria surveillance.

    Directory of Open Access Journals (Sweden)

    Yaw A Afrane

    Full Text Available BACKGROUND: Currently, intensive malaria control programs are being implemented in Africa to reduce the malaria burden. Clinical malaria data from hospitals are valuable for monitoring trends in malaria morbidity and for evaluating the impacts of these interventions. However, the reliability of hospital-based data for true malaria incidence is often questioned because of diagnosis accuracy issues and variation in access to healthcare facilities among sub-groups of the population. This study investigated how diagnosis and treatment practices of malaria cases in hospitals affect reliability of hospital malaria data. METHODOLOGY/PRINCIPAL FINDINGS: The study was undertaken in health facilities in western Kenya. A total of 3,569 blood smears were analyzed after being collected from patients who were requested by clinicians to go to the hospital's laboratory for malaria testing. We applied several quality control measures for clinical malaria diagnosis. We compared our slide reading results with those from the hospital technicians. Among the 3,390 patients whose diagnoses were analyzed, only 36% had clinical malaria defined as presence of any level of parasitaemia and fever. Sensitivity and specificity of clinicians' diagnoses were 60.1% (95% CI: 61.1-67.5 and 75.0% (95% CI: 30.8-35.7, respectively. Among the 980 patients presumptively treated with an anti-malarial by the clinicians without laboratory diagnosis, only 47% had clinical malaria. CONCLUSIONS/SIGNIFICANCE: These findings revealed substantial over-prescription of anti-malarials and misdiagnosis of clinical malaria. More than half of the febrile cases were not truly clinical malaria, but were wrongly diagnosed and treated as such. Deficiency in malaria diagnosis makes health facility data unreliable for monitoring trends in malaria morbidity and for evaluating impacts of malaria interventions. Improving malaria diagnosis should be a top priority in rural African health centers.

  4. Malaria: developing an action programme.

    Science.gov (United States)

    Seadzi, G K; Nyonator, F K

    1995-03-01

    Malaria is the most common reason that people seek medical care in Ghana. This situation is taken for granted by the people, and there is no organized prevention effort. A World Health Organization-sponsored pilot malaria eradication program (1958-64) was abandoned after a peak period of activity in 1963 when vector control included indoor spraying with DDT. Recently there has been an upward trend in the incidence of malaria, with 15% of all cases becoming complicated. The main vector species are A. gambiae, A. melas, and A. funestus, and the predominant parasite species is Plasmodium falciparum. Treatment of choice is chloroquine phosphate, and although drug resistance has been suspected, it has not been documented. All health facilities are stretched to the limit with regard to the diagnosis and treatment of malaria. Field research is needed to provide a more accurate picture of the current situation. The clinical ability to deliver prompt diagnoses and treatment must be strengthened, and public health education must be instituted. The regional health management system must be improved, and personnel must be taught to use collected data. The use of bed nets, which is common in the south, should be encouraged, and impregnated nets should be introduced.

  5. Malaria Chemoprophylaxis in Military Aircrew

    Science.gov (United States)

    2001-06-01

    for WHO Group 1I endemic deficiency, including macrocytic anemia , areas. aphthous ulcers, and stomatitis. - Chemoprophylaxis for WHO Group III endemic...deficiency is an absolute contraindication because of the risk of -- docetaxel (Taxotere®) hemolytic anemia . This defect is known to affect...headache shown such a property. - accommodation disorders - agranulocytosis, anemia and CONCLUSION methemoglobinemia The choice of malaria

  6. DNA Sensors for Malaria Diagnosis

    DEFF Research Database (Denmark)

    Hede, Marianne Smedegaard; Fjelstrup, Søren; Knudsen, Birgitta R.

    2015-01-01

    In the field of malaria diagnosis much effort is put into the development of faster and easier alternatives to the gold standard, blood smear microscopy. Nucleic acid amplification based techniques pose some of the most promising upcoming diagnostic tools due to their potential for high sensitivity...

  7. Chemical biology: Knockout for malaria

    Science.gov (United States)

    Krysiak, Joanna; Sieber, Stephan A.

    2014-02-01

    Discovering and validating new targets is urgently required to tackle the rise in resistance to antimalarial drugs. Now, inhibition of the enzyme N-myristoyltransferase has been shown to prevent the formation of a critical subcellular organelle in the parasite that causes malaria, leading to death of the parasite.

  8. President’s Malaria Initiative

    Science.gov (United States)

    2008-11-16

    the single most serious several projects on the bionomics and health hazard to Allied troops in the ecology of Anopheles in West Java, South Pacific...Malawi, Mozambique , (USAID) to train health workers in the Rwanda and Senegal were initiated, and diagnosis and control of malaria. I also in FY 2008

  9. 7 CFR 58.147 - Insect and rodent control program.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Insect and rodent control program. 58.147 Section 58... Service 1 Operations and Operating Procedures § 58.147 Insect and rodent control program. In addition to... made responsible for the performance of a regularly scheduled insect and rodent control...

  10. 7 CFR 58.247 - Insect and rodent control program.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Insect and rodent control program. 58.247 Section 58... Service 1 Operations and Operating Procedures § 58.247 Insect and rodent control program. In addition to... made responsible for the performance of a regularly scheduled insect and rodent control program...

  11. 20 CFR 654.415 - Insect and rodent control.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Insect and rodent control. 654.415 Section 654.415 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR SPECIAL... Insect and rodent control. Housing and facilities shall be free of insects, rodents, and other vermin....

  12. Prevalence of leptospirosis and toxoplasmosis: A study of rodents ...

    African Journals Online (AJOL)

    Leptospira and Toxoplasma infections in rodents and shrews in Mikese area of Morogoro ... Human and other animals such as rodents excluding cats are intermediate hosts of ..... Berdoy, M., Webster, J.P. & Macdonald, D.W. (2000) Fatal attraction in rats ... Rats, Mice and People: Rodent Biology and Management, 543-547.

  13. Malaria elimination in India and regional implications.

    Science.gov (United States)

    Wangdi, Kinley; Gatton, Michelle L; Kelly, Gerard C; Banwell, Cathy; Dev, Vas; Clements, Archie C A

    2016-10-01

    The malaria situation in India is complex as a result of diverse socio-environmental conditions. India contributes a substantial burden of malaria outside sub-Saharan Africa, with the third highest Plasmodium vivax prevalence in the world. Successful malaria control in India is likely to enhance malaria elimination efforts in the region. Despite modest gains, there are many challenges for malaria elimination in India, including: varied patterns of malaria transmission in different parts of the country demanding area-specific control measures; intense malaria transmission fuelled by favourable climatic and environment factors; varying degrees of insecticide resistance of vectors; antimalarial drug resistance; a weak surveillance system; and poor national coordination of state programmes. Prevention and protection against malaria are low as a result of a weak health-care system, as well as financial and socioeconomic constraints. Additionally, the open borders of India provide a potential route of entry for artesunate-resistant parasites from southeast Asia. This situation calls for urgent dialogue around tackling malaria across borders-between India's states and neighbouring countries-through sharing of information and coordinated control and preventive measures, if we are to achieve the aim of malaria elimination in the region. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Molecular imaging of neuroinflammation in preclinical rodent models using positron emission tomography.

    Science.gov (United States)

    Gargiulo, Sara; Coda, Anna R; Panico, Mariarosaria; Gramanzini, Matteo; Moresco, Rosa M; Chalon, Sylvie; Pappatà, Sabina

    2017-03-01

    Neuroinflammation (NI) is an adaptive response to different noxious stimuli, involving microglia, astrocytes and peripheral immune cells. NI is a hallmark of several acute and chronic diseases of central nervous system (CNS) and contributes to both damage and repair of CNS tissue. Interventional or genetically modified rodent models mimicking human neuropathologies may provide valuable insights on basic mechanisms of NI, but also for improving the development of new diagnostic and therapeutic strategies. Preclinical positron emission tomography (PET) allows to investigate noninvasively the inflammatory response in CNS of rodent models at a molecular level, validating innovative probes for early diagnosis, and characterizing the time course of neuroinflammatory changes and their relationship with disease progression, as well as the effects of experimental treatments with high translational potential. In particular, recent efforts of preclinical PET field are intended to develop specific and selective radiotracers that target the activation of innate immune system in CNS. Here, we have reviewed the state of art for PET in relevant rodent models of acute and chronic neuropathologies associated with NI, with particular regard on imaging of activated microglia and astrocytes.

  15. Laboratory diagnosis of malaria -- overview.

    Science.gov (United States)

    Bhatt, K M

    1994-01-01

    Features of the laboratory diagnosis of malaria are described. Microscope equipment is absolutely essential. Clinical symptoms are inadequate for the proper diagnosis of malaria. Screening for malaria involves identification of all cases where high fever is present in endemic areas. Diagnosis is complicated because many people take antimalarial drugs which reduce the chances of detecting malarial parasites. Confirmation should be made before treatment is administered. A thick blood slide can be quickly and cheaply taken without much training of health personnel. The disadvantage of thick stains is the difficulty in identifying "plasmodium" strains. When a thin smear with Giemsa and Leishmanin stain is used, a light infection may be missed. Thin smears require trained personnel and time, which in peak seasons may be impractical. Urinary tract and viral infections may be confused with malaria. Evidence of parasites can be discerned from thick stains. Modern assay techniques are also available. There are enzyme linked immunosorbent assays (ELISA) and immunofluorescent assay techniques (IFAT), which are frequently used in large scale seroepidemiological studies. DNA probes have the limitation of radioisotope handling problems. Acridine orange fluorescent microscopy with capillary centrifuged blood is a technique which improves the viability of Giemsa stain procedures. This technique is desirable because of the sensitivity and speed of diagnosis. The quantitative buddy coat (GBC) technique is superior to Giemsa stained thick blood film in identifying malaria, but it is not reliable with mixed infections. Advanced techniques are not readily available in local settings. The recommendation is to continue use of thick or thin blood film and trained health personnel. Laboratory results must be interpreted in the context of when the flood film was prepared, prior drug administration, and clinical manifestations.

  16. Predictive indices of empirical clinical diagnosis of malaria among under-five febrile children attending paediatric outpatient clinic

    Directory of Open Access Journals (Sweden)

    Hassan A Elechi

    2015-01-01

    Full Text Available Background: Malaria has remained an important public health problem in Nigeria with children under 5 years of age bearing the greatest burden. Accurate and prompt diagnosis of malaria is an important element in the fight against the scourge. Due to the several limitations of microscopy, diagnosis of malaria has continued to be made based on clinical ground against several World Health Organization (WHO recommendations. Thus, we aim to assess the performance of empirical clinical diagnosis among febrile children under 5 years of age in a busy pediatric outpatient clinic. Materials and Methods: The study was a cross-sectional study. Children aged <5 years with fever or 72 h history of fever were recruited. Children on antimalarial prophylaxis or on treatment for malaria were excluded. Relevant information was obtained from the caregiver and clinical note of the child using interviewer administered questionnaire. Two thick and two thin films were made, stained, and read for each recruited child. Data was analysed using SPSS version 16. Results: Of the 433 children studied, 98 (22.6% were empirically diagnosed as having malaria and antimalarial drug prescribed. Twenty-three (23.5% of these children were confirmed by microscopy to have malaria parasitemia, while 75 (76.5% were negative for malaria parasitemia. Empirical clinical diagnosis show poor predictive indices with sensitivity of 19.2%, specificity of 76.0%, positive predictive value of 23.5% and negative predictive value of 71%. Conclusion and Recommendations: Empirical clinical diagnosis of malaria among the under-five children with symptoms suggestive of acute malaria is highly not reliable and hence the need to strengthen parasitological diagnosis.

  17. Using Malaria Medication for Leg Cramps Is Risky

    Science.gov (United States)

    ... Products Vaccines, Blood & Biologics Articulos en Espanol Using Malaria Medication for Leg Cramps is Risky Printer-friendly ... approved only to treat a certain type of malaria (uncomplicated malaria) caused by the parasite Plasmodium falciparum. ...

  18. Malaria has no effect on birth weight in Rwanda

    NARCIS (Netherlands)

    Rulisa, S.; Mens, P.F.; Karema, C.; Schallig, H.D.F.H.; Kaligirwa, N.; Vyankandondera, J.; de Vries, P.J.

    2009-01-01

    Background: Malaria has a negative effect on pregnancy outcome, causing low birth weight, premature birth and stillbirths, particularly in areas with high malaria transmission. In Rwanda, malaria transmission intensity ranges from high to nil, probably associated with variable altitudes. Overall,

  19. Prevalence of malaria and patients in Ethiope E alence of malaria ...

    African Journals Online (AJOL)

    McRoy

    2014-12-31

    Dec 31, 2014 ... of Animal and Environmental Biology, Delta State University, Abraka, N pical Disease ... are capable of transmitting the human ..... seeking behaviour of young Nigerian adults. ... malaria parasites in culture. ... malaria in mice.

  20. COMPARATIVE STUDY OF RDTS v/s MICROSCOPY FOR THE DIAGNOSIS OF MALARIA IN CHILDREN

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    Rajesh Kumar

    2014-05-01

    Full Text Available Malaria presents a diagnostic challenge in most tropical countries. Rapid detection of the malaria parasite and early treatment of infection still remain the most important goals of disease management. Therefore, performance characteristics of the indigenous RDTs was determined among children with suspected malaria fever attending pediatrics OPD or admitted in indoor of UP RIMS n R Saifai central India, to assess whether this rapid diagnostic test (RDT could be used for diagnosis of malaria and results were compared with Gold Standard microscopy test. We also assessed the logical utilization of RDTs to monitor treatment outcome. MATERIALS AND METHODS: 03 months to 12 years old children who were presented with acute fever without any focus to the OPD or IPD of our department from May 2011 to April 2013 were selected for the study. A finger prick blood sample was collected from each clinically suspected case of malaria to prepare blood smear and for testing with the RDT after taking informed consent. The blood smears were read by an experienced microscopist blinded to the RDT results and clinical status of the subjects. The figures for specificity, sensitivity, accuracy and predictive values were calculated using microscopy as gold standard. RESULTS: Analysis revealed that overall sensitivity, specificity and accuracy of the RDT were approx. 90%, while RDT is useful to confirm the diagnosis of new symptomatic cases of suspected malaria infection, the persistence of parasite antigen leading to false positives even after clearance of asexual Parasitaemia has limited its utility as a prognostic tool. The study showed that RDTs was easy to use, reliable and cheap for diagnosing new malaria cases, and is an appropriate test for the use in the fields and remote areas.

  1. Concurrent malaria and typhoid fever in the tropics: the diagnostic challenges and public health implications

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    C.J. Uneke

    2008-05-01

    Full Text Available Background & objectives: Malaria and typhoid fever still remain diseases of major public health importance in the tropics. Individuals in areas endemic for both the diseases are at substantial risk of contracting both these diseases, either concurrently or an acute infection superimposed on a chronic one. The objective of this report was to systematically review scientific data from studies conducted in the tropics on concurrent malaria and typhoid fever within the last two decades (1987–2007, to highlight the diagnostic challenges and the public health implications. Methods: Using the MedLine Entrez-PubMed search, relevant publications were identified for the review via the key words Malaria and Typhoid fever, which yielded 287 entries as of January 2008. Results: Most of the studies reviewed expressed concern that poor diagnosis continues to hinder effective control of concurrent malaria and typhoid fever in the tropics due to: non-specific clinical presentation of the diseases; high prevalence of asymptomatic infections; lack of resources and insufficient access to trained health care providers and facilities; and widespread practice of self-treatment for clinically suspected malaria or typhoid fever. Interpretation & conclusion: There were considerably higher rates of concurrent malaria and typhoid fever by Widal test compared to the bacteriological culture technique. Although culture technique remains the gold standard in typhoid fever diagnosis, Widal test is still of significant diagnostic value provided judicious interpretation of the test is made against a background of pertinent information. Malaria could be controlled through interventions to minimize human-vector contact, while improved personal hygiene, targeted vaccination campaigns and intensive community health education could help to control typhoid fever in the tropics.

  2. Augmented particle trapping and attenuated inflammation in the liver by protective vaccination against Plasmodium chabaudi malaria

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    Dkhil Mohamed A

    2009-04-01

    Full Text Available Abstract Background To date all efforts to develop a malaria vaccine have failed, reflecting the still fragmentary knowledge about protective mechanisms against malaria. In order to evaluate if vaccination changes responses of the anti-malaria effectors spleen and liver to blood stage malaria, BALB/c mice succumbing to infection with Plasmodium chabaudi were compared to those surviving after vaccination. Methods Mice were vaccinated with host cell plasma membranes isolated from P. chabaudi-infected erythrocytes. Hepatic and splenic capacity to trap particulate material was determined after injection of fluorescent polystyrol beads. Hepatic gene expression was measured using real-time RT-PCR and Northern blotting. Results Survival of BALB/c mice was raised from 0% to 80% and peak parasitaemia was decreased by about 30% by vaccination. Vaccination boosted particle trapping capacity of the liver during crisis when splenic trapping is minimal due to spleen 'closing'. It also attenuated malaria-induced inflammation, thus diminishing severe damages and hence liver failure. Vaccination increased hepatic IFN-γ production but mitigated acute phase response. Vaccination has a complex influence on infection-induced changes in expression of hepatic nuclear receptors (CAR, FXR, RXR, and PXR and of the metabolic enzymes Sult2a and Cyp7a1. Although vaccination decreased CAR mRNA levels and prevented Cyp7a1 suppression by the CAR ligand 1,2-bis [2-(3,5-dichloropyridyloxy]benzene (TCPOBOP on day 8 p.i., Sult2a-induction by TCPOBOP was restored. Conclusion These data support the view that the liver is an essential effector site for a vaccine against blood stage malaria: vaccination attenuates malaria-induced inflammation thus improving hepatic metabolic activity and particle trapping activity of the liver.

  3. Perinatal kynurenine 3-hydroxylase inhibition in rodents: pathophysiological implications.

    Science.gov (United States)

    Ceresoli-Borroni, Gianpiera; Guidetti, Paolo; Amori, Laura; Pellicciari, Roberto; Schwarcz, Robert

    2007-03-01

    The kynurenine pathway (KP) of tryptophan degradation contains three neuroactive metabolites: the neuroinhibitory agent kynurenic acid (KYNA) and, in a competing branch, the free radical generator 3-hydroxykynurenine (3-HK) and the excitotoxin quinolinic acid (QUIN). These three "kynurenines" derive from a common precursor, L-kynurenine, and are recognized for their role in brain physiology and pathophysiology. Inhibition of kynurenine 3-hydroxylase, the enzyme responsible for 3-HK formation, shifts KP metabolism in the mature brain toward enhanced KYNA formation. We now tested the cerebral effects of kynurenine 3-hydroxylase inhibition in immature rodents. Rat pups treated with the kynurenine 3-hydroxylase inhibitor UPF 648 (30 mg/kg, i.p.) 10 min after birth showed substantial increases in cerebral and liver kynurenine and KYNA levels up to 24 hr later, whereas 3-HK and QUIN levels were simultaneously decreased. Administered to pregnant rats or mice on the last day of gestation, UPF 648 (50 mg/kg, i.p.) produced qualitatively similar changes (i.e., large increases in kynurenine and KYNA and reductions in 3-HK and QUIN) in the brain and liver of the offspring. Rat pups delivered by UPF 648-treated mothers and immediately exposed to neonatal asphyxia showed further enhanced brain KYNA levels. These studies demonstrate that acute kynurenine 3-hydroxylase inhibition effectively shifts cerebral KP metabolism in neonatal rodents toward increased KYNA formation. Selective inhibitors of this enzyme may therefore provide neuroprotection in newborns and will also be useful for the experimental evaluation of the long-term effects of perinatal KP impairment.

  4. Central melanopsin projections in the diurnal rodent, Arvicanthis niloticus.

    Science.gov (United States)

    Langel, Jennifer L; Smale, Laura; Esquiva, Gema; Hannibal, Jens

    2015-01-01

    The direct effects of photic stimuli on behavior are very different in diurnal and nocturnal species, as light stimulates an increase in activity in the former and a decrease in the latter. Studies of nocturnal mice have implicated a select population of retinal ganglion cells that are intrinsically photosensitive (ipRGCs) in mediation of these acute responses to light. ipRGCs are photosensitive due to the expression of the photopigment melanopsin; these cells use glutamate and pituitary adenylate cyclase-activating polypeptide (PACAP) as neurotransmitters. PACAP is useful for the study of central ipRGC projections because, in the retina, it is found exclusively within melanopsin cells. Little is known about the central projections of ipRGCs in diurnal species. Here, we first characterized these cells in the retina of the diurnal Nile grass rat using immunohistochemistry (IHC). The same basic subtypes of melanopsin cells that have been described in other mammals were present, but nearly 25% of them were displaced, primarily in its superior region. PACAP was present in 87.7% of all melanopsin cells, while 97.4% of PACAP cells contained melanopsin. We then investigated central projections of ipRGCs by examining the distribution of immunoreactive PACAP fibers in intact and enucleated animals. This revealed evidence that these cells project to the suprachiasmatic nucleus, lateral geniculate nucleus (LGN), pretectum, and superior colliculus. This distribution was confirmed with injections of cholera toxin subunit β coupled with Alexa Fluor 488 in one eye and Alexa Fluor 594 in the other, combined with IHC staining of PACAP. These studies also revealed that the ventral and dorsal LGN and the caudal olivary pretectal nucleus receive less innervation from ipRGCs than that reported in nocturnal rodents. Overall, these data suggest that although ipRGCs and their projections are very similar in diurnal and nocturnal rodents, they may not be identical.

  5. Central melanopsin projections in the diurnal rodent, Arvicanthis niloticus

    Directory of Open Access Journals (Sweden)

    Jennifer Lou Langel

    2015-07-01

    Full Text Available The direct effects of photic stimuli on behavior are very different in diurnal and nocturnal species, as light stimulates an increase in activity in the former and a decrease in the latter. Studies of nocturnal mice have implicated a select population of retinal ganglion cells that are intrinsically photosensitive (ipRGCs in mediation of these acute responses to light. ipRGCs are photosensitive due to the expression of the photopigment melanopsin; these cells use glutamate and pituitary adenylate cyclase-activating polypeptide (PACAP as neurotransmitters. PACAP is useful for the study of central ipRGC projections because, in the retina, it is found exclusively within melanopsin cells. Little is known about the central projections of ipRGCs in diurnal species. Here, we first characterized these cells in the retina of the diurnal Nile grass rat using immunohistochemistry (IHC. The same basic subtypes of melanopsin cells that have been described in other mammals were present, but nearly 25% of them were displaced, primarily in its superior region. PACAP was present in 87.7% of all melanopsin cells, while 97.4% of PACAP cells contained melanopsin. We then investigated central projections of ipRGCs by examining the distribution of immunoreactive PACAP fibers in intact and enucleated animals. This revealed evidence that these cells project to the suprachiasmatic nucleus, lateral geniculate nucleus (LGN, pretectum and superior colliculus. This distribution was confirmed with injections of cholera toxin subunit β coupled with Alexa Fluor 488 in one eye and Alexa Flour 594 in the other, combined with IHC staining of PACAP. These studies also revealed that the ventral and dorsal LGN and the caudal olivary pretectal nucleus receive less innervation from ipRGCs than that reported in nocturnal rodents. Overall, these data suggest that although ipRGCs and their projections are very similar in diurnal and nocturnal rodents, they may not be identical.

  6. From "forest malaria" to "bromeliad malaria": a case-study of scientific controversy and malaria control.

    Science.gov (United States)

    Gadelha, P

    1994-08-01

    The article analyses the evolution of knowledge and rationale of control of a special case of malaria transmission based on Bromelia-Kerteszia complex. Since bromeliaceae function as a 'host of the carrier' and were previously associated with natural forests, the elucidation of bromeliad malaria historically elicited controversies concerning the imputation of Kertesziae as transmitters as well as over control strategies directed to bromelia eradication (manual removal, herbicides and deforestation), use of insecticides and chemoprophylaxis. Established authority, disciplinary traditions, conceptual premises and contemporary criteria for validating knowledge in the field partly explain the long time gap since Adolpho Lutz announced at the beginning of the century the existence of a new mosquito and breeding site as responsible for a 'forest malaria' epidemic occurring at a high altitude. The article brings attention to how economic, political and institutional determinants played an important role in redefining studies that led both in Trinidad and Brazil to the recognition of the importance of kerteszia transmission, including urban areas, and establishing new approaches to its study, most relevant of all the concurrence of broad ecological research. The article then describes the Brazilian campaign strategies which showed significant short-term results but had to wait four decades to achieve the goal of eradication due to the peculiar characteristics of this pathogenic complex. Finally, it brings attention to the importance of encompassing social values and discourses, in this case, environmental preservation, to understanding historical trends of malaria control programs.

  7. Evidence of human hantavirus infection and zoonotic investigation of hantavirus prevalence in rodents in western Java, Indonesia.

    Science.gov (United States)

    Kosasih, Herman; Ibrahim, Ima Nurisa; Wicaksana, Rudi; Alisjahbana, Bachti; Hoo, Yumilia; Yo, Iing H; Antonjaya, Ungke; Widjaja, Susana; Winoto, Imelda; Williams, Maya; Blair, Patrick J

    2011-06-01

    During febrile surveillance in the western Java City of Bandung, Indonesia, a patient with clinical symptoms consistent with hantavirus infection was found to have elevated titers of hantavirus-specific immunoglobulin M (IgM) and IgG antibodies. A subsequent epizoological investigation demonstrated a higher prevalence of hantavirus IgG antibodies in rodents trapped in the vicinity of the patient's home compared with rodents from a control area (13.2% vs. 4.7%, p = 0.036). The Old World Seoul hantavirus was detected by reverse transcriptase-polymerase chain reaction in the organs of 71% of the seropositive rodents tested. This is the first report of a Seoul virus infection in Indonesia supported by clinical, serological, and epizoological evidences. These findings suggest that hantavirus infection should be on the clinical differential diagnosis when acutely ill febrile patients report for care in western Java.

  8. Herbs and herbal combinations used to treat suspected malaria in Bo, Sierra Leone.

    Science.gov (United States)

    Ranasinghe, Shamika; Ansumana, Rashid; Lamin, Joseph M; Bockarie, Alfred S; Bangura, Umaru; Buanie, Jacob A G; Stenger, David A; Jacobsen, Kathryn H

    2015-05-26

    Most adults in West Africa treat acute febrile illnesses with local herbs, but the patterns of herbs used for malaria have not been recently described in Sierra Leone. We used a population-based cross-sectional approach to interview 810 randomly-sampled rural and urban adult residents of Bo, Sierra Leone, in December 2013 and January 2014 about their use of herbal remedies when they suspect they have malaria. In total, 55% of the participants reported taking one or more of seven herbs to treat symptoms of malaria. Among herb users, the most commonly used anti-malarial herbs were Moringa oleifera (moringa, 52%) and Sarcocephalus latifolius (yumbuyambay, 50%). The other herbs used included Senna siamea (shekutoure, 18%), Cassia sieberiana (gbangba, 18%), Uvaria afzelii (gone-botai, 14%), Morinda chrysorhiza (njasui, 14%), and Craterispermum laurinum (nyelleh, 7%). Combination herbal therapy was common, with 37% of herb users taking two or more herbs together when ill with suspected malaria. Indigenous medical knowledge about herbal remedies and combinations of local herbs remains an integral part of malaria case management in Sierra Leone. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. Complement activation in Ghanaian children with severe Plasmodium falciparum malaria

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    Ofori Michael F

    2007-12-01

    Full Text Available Abstract Background Severe anaemia (SA, intravascular haemolysis (IVH and respiratory distress (RD are severe forms of Plasmodium falciparum malaria, with RD reported to be of prognostic importance in African children with malarial anaemia. Complement factors have been implicated in the mechanism leading to excess anaemia in acute P. falciparum infection. Methods The direct Coombs test (DCT and flow cytometry were used to investigate the mean levels of RBC-bound complement fragments (C3d and C3bαβ and the regulatory proteins [complement receptor 1 (CD35 and decay accelerating factor (CD55] in children with discrete clinical forms of P. falciparum malaria. The relationship between the findings and clinical parameters including coma, haemoglobin (Hb levels and RD were investigated. Results Of the 484 samples tested, 131(27% were positive in DCT, out of which 115/131 (87.8% were positive for C3d alone while 16/131 (12.2% were positive for either IgG alone or both. 67.4% of the study population were below 5 years of age and DCT positivity was more common in this age group relative to children who were 5 years or older (Odds ratio, OR = 3.8; 95%CI, 2.2–6.7, p Conclusion These results suggest that complement activation contributed to anaemia in acute childhood P. falciparum malaria, possibly through induction of erythrophagocytosis and haemolysis. In contrast to other studies, this study did not find association between levels of the complement regulatory proteins, CD35 and CD55 and malarial anaemia. These findings suggest that complement activation could also be involved in the pathogenesis of RD but larger studies are needed to confirm this finding.

  10. Distinct host cell fates for human malignant melanoma targeted by oncolytic rodent parvoviruses.

    Science.gov (United States)

    Vollmers, Ellen M; Tattersall, Peter

    2013-11-01

    The rodent parvoviruses are known to be oncoselective, and lytically infect many transformed human cells. Because current therapeutic regimens for metastatic melanoma have low response rates and have little effect on improving survival, this disease is a prime candidate for novel approaches to therapy, including oncolytic parvoviruses. Screening of low-passage, patient-derived melanoma cell lines for multiplicity-dependent killing by a panel of five rodent parvoviruses identified LuIII as the most melanoma-lytic. This property was mapped to the LuIII capsid gene, and an efficiently melanoma tropic chimeric virus shown to undergo three types of interaction with primary human melanoma cells: (1) complete lysis of cultures infected at very low multiplicities; (2) acute killing resulting from viral protein synthesis and DNA replication, without concomitant expansion of the infection, due to failure to export progeny virions efficiently; or (3) complete resistance that operates at an intracellular step following virion uptake, but preceding viral transcription.

  11. The role of vitamin D in malaria.

    Science.gov (United States)

    Lương, Khanh Vinh Quốc; Nguyễn, Lan Thi Hoàng

    2015-01-15

    An abnormal calcium-parathyroid hormone (PTH)-vitamin D axis has been reported in patients with malaria infection. A role for vitamin D in malaria has been suggested by many studies. Genetic studies have identified numerous factors that link vitamin D to malaria, including human leukocyte antigen genes, toll-like receptors, heme oxygenase-1, angiopoietin-2, cytotoxic T lymphocyte antigen-4, nucleotide-binding oligomerization domain-like receptors, and Bcl-2. Vitamin D has also been implicated in malaria via its effects on the Bacillus Calmette-Guerin (BCG) vaccine, matrix metalloproteinases, mitogen-activated protein kinase pathways, prostaglandins, reactive oxidative species, and nitric oxide synthase. Vitamin D may be important in malaria; therefore, additional research on its role in malaria is needed.

  12. Shrinking the malaria map: progress and prospects

    Science.gov (United States)

    Feachem, Richard GA; Phillips, Allison A; Hwang, Jimee; Cotter, Chris; Wielgosz, Benjamin; Greenwood, Brian M; Sabot, Oliver; Rodriguez, Mario Henry; Abeyasinghe, Rabindra R; Ghebreyesus, Tedros Adhanom; Snow, Robert W

    2010-01-01

    Summary In the past 150 years, roughly half of the countries in the world eliminated malaria. Nowadays, there are 99 endemic countries—67 are controlling malaria and 32 are pursuing an elimination strategy. This four-part Series presents evidence about the technical, operational, and financial dimensions of malaria elimination. The first paper in this Series reviews definitions of elimination and the state that precedes it: controlled low-endemic malaria. Feasibility assessments are described as a crucial step for a country transitioning from controlled low-endemic malaria to elimination. Characteristics of the 32 malaria-eliminating countries are presented, and contrasted with countries that pursued elimination in the past. Challenges and risks of elimination are presented, including Plasmodium vivax, resistance in the parasite and mosquito populations, and potential resurgence if investment and vigilance decrease. The benefits of elimination are outlined, specifically elimination as a regional and global public good. Priorities for the next decade are described. PMID:21035842

  13. Progress towards malaria control targets in relation to national malaria programme funding

    NARCIS (Netherlands)

    E.L. Korenromp (Eline); M. Hosseini (Mehran); R.D. Newman (Robert D); R.E. Cibulskis (Richard E)

    2013-01-01

    textabstractBackground: Malaria control has been dramatically scaled up the past decade, mainly thanks to increasing international donor financing since 2003. This study assessed progress up to 2010 towards global malaria impact targets, in relation to Global Fund, other donor and domestic malaria

  14. Progress towards malaria control targets in relation to national malaria programme funding

    NARCIS (Netherlands)

    E.L. Korenromp (Eline); M. Hosseini (Mehran); R.D. Newman (Robert D); R.E. Cibulskis (Richard E)

    2013-01-01

    textabstractBackground: Malaria control has been dramatically scaled up the past decade, mainly thanks to increasing international donor financing since 2003. This study assessed progress up to 2010 towards global malaria impact targets, in relation to Global Fund, other donor and domestic malaria p

  15. STUDY OF CLINICAL, HAEMATOLOGICAL AND HEPATIC MANIFESTATIONS IN PATIENTS WITH FALCIPARUM MALARIA

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    Balaraj

    2014-05-01

    Full Text Available OBJECTIVE: Malarial infection is a major health problem in many parts of India. Several factors have been attributed to increased morbidity and mortality in malaria with altered hematological and hepatic parameters playing an important role. Our aim is to study the clinical, hematological and hepatic manifestations in patients with falciparum malaria. METHODS: This observational study was conducted from November 2012 to October 2013 at Kempegowda Institute of Medical Science and Research Hospital Bangalore. 75 patients of falciparum malaria confirmed by PS, MPQBC positive for Plasmodium falciparum or both falciparum and vivax were included in the study. All patients underwent detailed clinical history, thorough physical examination and investigated with hematological and hepatic parameters. This was followed by monitoring the outcome of the patients with respect to morbidity and mortality. Data was analyzed with descriptive statistical tools. RESULT: Of the 75 patients fever was present in all cases. Pallor (62% was the most common sign followed by splenomegaly (58% and icterus (48%. Anemia (60% was the most common complication, followed by jaundice (44%, cerebral malaria (40%, ARF (25%, ARDS (12%. 12 patients had severe anemia (Hb% <6 gm %. Severe thrombocytopenia (<50, 000 mm3 was seen in 5% of the patients. PT and APTT were increased in 23% and 12% of the cases respectively. 2 patients in the study expired. CONCLUSION: Clinical manifestations of plasmodium falciparum infection ranged from only fever to severe complications including cerebral malaria, acute renal failure, acute hemolytic crisis and hepatic dysfunction. Acute onset fever and splenomegaly were most common clinical manifestations found. Severe Anemia and jaundice are poor prognostic factor and has adverse outcome. Thrombocytopenia increased PT; aPTT does not have any correlation to mortality

  16. Association of Heme Oxygenase 1 with Lung Protection in Malaria-Associated ALI/ARDS

    Science.gov (United States)

    Pereira, Marcelo L. M.; Ortolan, Luana S.; Sercundes, Michelle K.; Debone, Daniela; Murillo, Oscar; Lima, Flávia A.

    2016-01-01

    Malaria is a serious disease, caused by the parasite of the genus Plasmodium, which was responsible for 440,000 deaths in 2015. Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is one of the main clinical complications in severe malaria. The murine model DBA/2 reproduces the clinical signs of ALI/ARDS in humans, when infected with Plasmodium berghei ANKA. High levels of HO-1 were reported in cases of severe malaria. Our data indicated that the HO-1 mRNA and protein expression are increased in mice that develop malaria-associated ALI/ARDS (MA-ALI/ARDS). Additionally, the hemin, a HO-1 inducing drug, prevented mice from developing MA-ALI/ARDS when administered prior to the development of MA-ALI/ARDS in this model. Also, hemin treatment showed an amelioration of respiratory parameters in mice, high VEGF levels in the sera, and a decrease in vascular permeability in the lung, which are signs of ALI/ARDS. Therefore, the induction of HO-1 before the development of MA-ALI/ARDS could be protective. However, the increased expression of HO-1 on the onset of MA-ALI/ARDS development may represent an effort to revert the phenotype of this syndrome by the host. We therefore confirm that HO-1 inducing drugs could be used for prevention of MA-ALI/ARDS in humans. PMID:27974865

  17. Expression of cleaved caspase-3 in renal tubular cells in Plasmodium falciparum malaria patients.

    Science.gov (United States)

    Wichapoon, Benjamas; Punsawad, Chuchard; Viriyavejakul, Parnpen

    2017-01-01

    In Plasmodium falciparum malaria, the clinical manifestation of acute kidney injury (AKI) is commonly associated with acute tubular necrosis (ATN) in the kidney tissues. Renal tubular cells often exhibit various degrees of cloudy swelling, cell degeneration, and frank necrosis. To study individual cell death, this study evaluates the degree of renal tubular necrosis in association with apoptosis in malarial kidneys. Kidney tissues from P. falciparum malaria with AKI (10 cases), and without AKI (10 cases) were evaluated for tubular pathology. Normal kidney tissues from 10 cases served as controls. Tubular necrosis was assessed quantitatively in kidney tissues infected with P. falciparum malaria, based on histopathological evaluation. In addition, the occurrence of apoptosis was investigated using cleaved caspase-3 marker. Correlation between tubular necrosis and apoptosis was analyzed. Tubular necrosis was found to be highest in P. falciparum malaria patients with AKI (36.44% ± 3.21), compared to non-AKI (15.88% ± 1.63) and control groups (2.58% ± 0.39) (all p < 0.001). In the AKI group, the distal tubules showed a significantly higher degree of tubular necrosis than the proximal tubules (p = 0.021) and collecting tubules (p = 0.033). Tubular necrosis was significantly correlated with the level of serum creatinine (r = 0.596, p = 0.006), and the occurrence of apoptosis (r = 0.681, p = 0.001). In malarial AKI, the process of apoptosis occurs in ATN. © 2016 Asian Pacific Society of Nephrology.

  18. Predictive criteria to study the pathogenesis of malaria-associated ALI/ARDS in mice.

    Science.gov (United States)

    Ortolan, Luana S; Sercundes, Michelle K; Barboza, Renato; Debone, Daniela; Murillo, Oscar; Hagen, Stefano C F; Russo, Momtchilo; D' Império Lima, Maria Regina; Alvarez, José M; Amaku, Marcos; Marinho, Claudio R F; Epiphanio, Sabrina

    2014-01-01

    Malaria-associated acute lung injury/acute respiratory distress syndrome (ALI/ARDS) often results in morbidity and mortality. Murine models to study malaria-associated ALI/ARDS have been described; we still lack a method of distinguishing which mice will develop ALI/ARDS before death. This work aimed to characterize malaria-associated ALI/ARDS in a murine model and to demonstrate the first method to predict whether mice are suffering from ALI/ARDS before death. DBA/2 mice infected with Plasmodium berghei ANKA developing ALI/ARDS or hyperparasitemia (HP) were compared using histopathology, PaO2 measurement, pulmonary X-ray, breathing capacity, lung permeability, and serum vascular endothelial growth factor (VEGF) levels according to either the day of death or the suggested predictive criteria. We proposed a model to predict malaria-associated ALI/ARDS using breathing patterns (enhanced pause and frequency respiration) and parasitemia as predictive criteria from mice whose cause of death was known to retrospectively diagnose the sacrificed mice as likely to die of ALI/ARDS as early as 7 days after infection. Using this method, we showed increased VEGF levels and increased lung permeability in mice predicted to die of ALI/ARDS. This proposed method for accurately identifying mice suffering from ALI/ARDS before death will enable the use of this model to study the pathogenesis of this disease.

  19. Predictive Criteria to Study the Pathogenesis of Malaria-Associated ALI/ARDS in Mice

    Directory of Open Access Journals (Sweden)

    Luana S. Ortolan

    2014-01-01

    Full Text Available Malaria-associated acute lung injury/acute respiratory distress syndrome (ALI/ARDS often results in morbidity and mortality. Murine models to study malaria-associated ALI/ARDS have been described; we still lack a method of distinguishing which mice will develop ALI/ARDS before death. This work aimed to characterize malaria-associated ALI/ARDS in a murine model and to demonstrate the first method to predict whether mice are suffering from ALI/ARDS before death. DBA/2 mice infected with Plasmodium berghei ANKA developing ALI/ARDS or hyperparasitemia (HP were compared using histopathology, PaO2 measurement, pulmonary X-ray, breathing capacity, lung permeability, and serum vascular endothelial growth factor (VEGF levels according to either the day of death or the suggested predictive criteria. We proposed a model to predict malaria-associated ALI/ARDS using breathing patterns (enhanced pause and frequency respiration and parasitemia as predictive criteria from mice whose cause of death was known to retrospectively diagnose the sacrificed mice as likely to die of ALI/ARDS as early as 7 days after infection. Using this method, we showed increased VEGF levels and increased lung permeability in mice predicted to die of ALI/ARDS. This proposed method for accurately identifying mice suffering from ALI/ARDS before death will enable the use of this model to study the pathogenesis of this disease.

  20. [Research progress on malaria vector control].

    Science.gov (United States)

    Zhu, Guo-Ding; Cao, Jun; Zhou, Hua-Yun; Gao, Qi

    2013-06-01

    Vector control plays a crucial role in the stages of malaria control and elimination. Currently, it mainly relies on the chemical control methods for adult mosquitoes in malaria endemic areas, however, it is undergoing the serious threat by insecticide resistance. In recent years, the transgenic technologies of malaria vectors have made a great progress in the laboratory. This paper reviews the challenges of the traditional methods and the rapid developed genetic modified technology in the application of vector control.

  1. Towards seasonal forecasting of malaria in India.

    Science.gov (United States)

    Lauderdale, Jonathan M; Caminade, Cyril; Heath, Andrew E; Jones, Anne E; MacLeod, David A; Gouda, Krushna C; Murty, Upadhyayula Suryanarayana; Goswami, Prashant; Mutheneni, Srinivasa R; Morse, Andrew P

    2014-08-10

    Malaria presents public health challenge despite extensive intervention campaigns. A 30-year hindcast of the climatic suitability for malaria transmission in India is presented, using meteorological variables from a state of the art seasonal forecast model to drive a process-based, dynamic disease model. The spatial distribution and seasonal cycles of temperature and precipitation from the forecast model are compared to three observationally-based meteorological datasets. These time series are then used to drive the disease model, producing a simulated forecast of malaria and three synthetic malaria time series that are qualitatively compared to contemporary and pre-intervention malaria estimates. The area under the Relative Operator Characteristic (ROC) curve is calculated as a quantitative metric of forecast skill, comparing the forecast to the meteorologically-driven synthetic malaria time series. The forecast shows probabilistic skill in predicting the spatial distribution of Plasmodium falciparum incidence when compared to the simulated meteorologically-driven malaria time series, particularly where modelled incidence shows high seasonal and interannual variability such as in Orissa, West Bengal, and Jharkhand (North-east India), and Gujarat, Rajastan, Madhya Pradesh and Maharashtra (North-west India). Focusing on these two regions, the malaria forecast is able to distinguish between years of "high", "above average" and "low" malaria incidence in the peak malaria transmission seasons, with more than 70% sensitivity and a statistically significant area under the ROC curve. These results are encouraging given that the three month forecast lead time used is well in excess of the target for early warning systems adopted by the World Health Organization. This approach could form the basis of an operational system to identify the probability of regional malaria epidemics, allowing advanced and targeted allocation of resources for combatting malaria in India.

  2. The evolution of drug-resistant malaria

    OpenAIRE

    Plowe, Christopher V.

    2008-01-01

    Molecular epidemiological investigations have uncovered the patterns of emergence and global spread of Plasmodium falciparum resistance to chloroquine and sulfadoxine-pyrimethamine. Malaria parasites highly resistant to chloroquine and pyrimethamine spread from Asian origins to Africa, at great cost to human health and life. If artemisinin-resistant falciparum malaria follows the same pattern, renewed efforts to eliminate and eradicate malaria will be gravely threatened. This paper, adapted f...

  3. HIPOGLIKEMIA PADA SEORANG PENDERITA MALARIA

    Directory of Open Access Journals (Sweden)

    P. N. Harianto

    2012-09-01

    Full Text Available Hypoglycemia is a serious and often fatal complication of severe malaria. This condition has been reported in many parts of the world including from Thailand (1983 and from Indonesia by Hoffman (1988 and Harianto (1990. Two main causes that can lead to development of this condition are quinine administration and the severity of the malaria condition itself. A case study is presented about development of prolonged hypoglycemia after quinine administration. A 41 years old male was hospitalized with 4 days history of fever, headache vomiting and icterus. On examination he was found to be in good mental status, had a normal blood pressure, and a body temperature of 40°C. He also had icterus and hepatomegaly. Laboratory examination on admission showed malaria slide positive forRfalciparum ring 30-40, with parasite count of 3% (+ on day I. CBC showed: WBC of 21,700/mm3 and platelet count of 40,000/mm3. Blood chemistry showed glucose level of 77 mm %, serum bilirubin of 29.34 mg % (direct 21.87 mg % SGOT 31 u/l, SGPT 20 u/l, serum ureum 167 mg %, creatinine of 3.36 mg %, serum Na 123 m Eq/L and K 3.99 Eq/L. Urinalysis was normal except for specific gravity of 1.07. After diagnosis of bilious malaria was confirmed, the patient was given i.v. quinine 500 mg diluted in 500 ml 5% dextrose, infused over 4 hours and repeated every 8 hours. On day IVi.v. quinine was switched to oral preparation of 600 mg given bid and the next day quinine was changed to oral chloroquine. The day after admission (30 hours after quinine administration, blood glucose dropped to 21 mg %, 16-46 mg % on day III, and to less than 10 mg % on day IV. It gradulty returned to normal afterwards. Administration of 10% dextrose and boluses of 40% glucose were able to keep the patient in good clinical condition and prevent death. Malaria slide improved on day III, became negative by day IV and serum bilirubin also decreased on follow up. Hypoglycemia should be expected in severe malaria

  4. Effect of preventive supplementation with zinc and other micronutrients on malaria and diarrhoeal morbidity in African children

    NARCIS (Netherlands)

    Veenemans, J.

    2011-01-01

    Background: Zinc is important for innate and adaptive immune responses to infection. Preventive zinc supplementation has been shown to reduce the incidence of acute diarrhoea by 20%. Few trials have evaluated its effect against malaria. Because trial results for both outcomes are inconsistent,

  5. Molecular epidemiology of paramyxoviruses in Zambian wild rodents and shrews.

    Science.gov (United States)

    Sasaki, Michihito; Muleya, Walter; Ishii, Akihiro; Orba, Yasuko; Hang'ombe, Bernard M; Mweene, Aaron S; Moonga, Ladslav; Thomas, Yuka; Kimura, Takashi; Sawa, Hirofumi

    2014-02-01

    Rodents and shrews are known to harbour various viruses. Paramyxoviruses have been isolated from Asian and Australian rodents, but little is known about them in African rodents. Recently, previously unknown paramyxovirus sequences were found in South African rodents. To date, there have been no reports related to the presence and prevalence of paramyxoviruses in shrews. We found a high prevalence of paramyxoviruses in wild rodents and shrews from Zambia. Semi-nested reverse transcription-PCR assays were used to detect paramyxovirus RNA in 21 % (96/462) of specimens analysed. Phylogenetic analysis revealed that these viruses were novel paramyxoviruses and could be classified as morbillivirus- and henipavirus-related viruses, and previously identified rodent paramyxovirus-related viruses. Our findings suggest the circulation of previously unknown paramyxoviruses in African rodents and shrews, and provide new information regarding the geographical distribution and genetic diversity of paramyxoviruses.

  6. Redefining an epitope of a malaria vaccine candidate, with antibodies against the N-terminal MSA-2 antigen of Plasmodium harboring non-natural peptide bonds.

    Science.gov (United States)

    Lozano, José Manuel; Guerrero, Yuly Andrea; Alba, Martha Patricia; Lesmes, Liliana Patricia; Escobar, José Oswaldo; Patarroyo, Manuel Elkin

    2013-10-01

    The aim of obtaining novel vaccine candidates against malaria and other transmissible diseases can be partly based on selecting non-polymorphic peptides from relevant antigens of pathogens, which have to be then precisely modified for inducing a protective immunity against the disease. Bearing in mind the high degree of the MSA-2(21-40) peptide primary structure's genetic conservation among malaria species, and its crucial role in the high RBC binding ability of Plasmodium falciparum (the main agent causing malaria), structurally defined probes based on non-natural peptide-bond isosteres were thus designed. Thus, two peptide mimetics were obtained (so-called reduced amide pseudopeptides), in which naturally made amide bonds of the (30)FIN(32)-binding motif of MSA-2 were replaced with ψ-[CH2-NH] methylene amide isostere bonds, one between the F-I and the second between I-N amino acid pairs, respectively, coded as ψ-128 ψ-130. These peptide mimetics were used to produce poly- and monoclonal antibodies in Aotus monkeys and BALB/c mice. Parent reactive mice-derived IgM isotype cell clones were induced to Ig isotype switching to IgG sub-classes by controlled in vitro immunization experiments. These mature isotype immunoglobulins revealed a novel epitope in the MSA-2(25-32) antigen and two polypeptides of rodent malaria species. Also, these antibodies' functional activity against malaria was tested by in vitro assays, demonstrating high efficacy in controlling infection and evidencing neutralizing capacity for the rodent in vivo malaria infection. The neutralizing effect of antibodies induced by site-directed designed peptide mimetics on Plasmodium's biological development make these pseudopeptides a valuable tool for future development of immunoprophylactic strategies for controlling malarial infection.

  7. Rodent reservoirs of future zoonotic diseases.

    Science.gov (United States)

    Han, Barbara A; Schmidt, John Paul; Bowden, Sarah E; Drake, John M

    2015-06-02

    The increasing frequency of zoonotic disease events underscores a need to develop forecasting tools toward a more preemptive approach to outbreak investigation. We apply machine learning to data describing the traits and zoonotic pathogen diversity of the most speciose group of mammals, the rodents, which also comprise a disproportionate number of zoonotic disease reservoirs. Our models predict reservoir status in this group with over 90% accuracy, identifying species with high probabilities of harboring undiscovered zoonotic pathogens based on trait profiles that may serve as rules of thumb to distinguish reservoirs from nonreservoir species. Key predictors of zoonotic reservoirs include biogeographical properties, such as range size, as well as intrinsic host traits associated with lifetime reproductive output. Predicted hotspots of novel rodent reservoir diversity occur in the Middle East and Central Asia and the Midwestern United States.

  8. Bats and Rodents Shape Mammalian Retroviral Phylogeny.

    Science.gov (United States)

    Cui, Jie; Tachedjian, Gilda; Wang, Lin-Fa

    2015-11-09

    Endogenous retroviruses (ERVs) represent past retroviral infections and accordingly can provide an ideal framework to infer virus-host interaction over their evolutionary history. In this study, we target high quality Pol sequences from 7,994 Class I and 8,119 Class II ERVs from 69 mammalian genomes and surprisingly find that retroviruses harbored by bats and rodents combined occupy the major phylogenetic diversity of both classes. By analyzing transmission patterns of 30 well-defined ERV clades, we corroborate the previously published observation that rodents are more competent as originators of mammalian retroviruses and reveal that bats are more capable of receiving retroviruses from non-bat mammalian origins. The powerful retroviral hosting ability of bats is further supported by a detailed analysis revealing that the novel bat gammaretrovirus, Rhinolophus ferrumequinum retrovirus, likely originated from tree shrews. Taken together, this study advances our understanding of host-shaped mammalian retroviral evolution in general.

  9. Homeobox Genes in the Rodent Pineal Gland

    DEFF Research Database (Denmark)

    Rath, Martin Fredensborg; Rohde, Kristian; Klein, David C

    2013-01-01

    The pineal gland is a neuroendocrine gland responsible for nocturnal synthesis of melatonin. During early development of the rodent pineal gland from the roof of the diencephalon, homeobox genes of the orthodenticle homeobox (Otx)- and paired box (Pax)-families are expressed and are essential...... for normal pineal development consistent with the well-established role that homeobox genes play in developmental processes. However, the pineal gland appears to be unusual because strong homeobox gene expression persists in the pineal gland of the adult brain. Accordingly, in addition to developmental...... functions, homeobox genes appear to be key regulators in postnatal phenotype maintenance in this tissue. In this paper, we review ontogenetic and phylogenetic aspects of pineal development and recent progress in understanding the involvement of homebox genes in rodent pineal development and adult function...

  10. Malaria in three epidemiological strata in Mauritania.

    Science.gov (United States)

    Ouldabdallahi Moukah, Mohamed; Ba, Ousmane; Ba, Hampaté; Ould Khairy, Mohamed Lemine; Faye, Ousmane; Bogreau, Hervé; Simard, Frédéric; Basco, Leonardo K

    2016-04-12

    Malaria epidemiology in Mauritania has been characterized on the basis of epidemiological strata, defined by climatic and geographic features, which divide the country into three zones: Sahelian zone, Sahelo-Saharan transition zone, and Saharan zone. The association between geographic stratification and malaria transmission was assessed through a series of parasitological and entomological surveys. Surveys were conducted during the 'cool' dry season in 2011, 'hot' dry season in 2012, and rainy season in 2013 in a total of 12 sentinel sites. Finger-prick capillary blood samples were collected from children aged 2-9 years old in randomly selected households for microscopic examination and rapid diagnostic test for malaria. Adult mosquitoes were sampled by pyrethrum spray catch and CDC light traps and identified using morphological keys and molecular tools. Of 3445 children included, 143 (4.15 %) were infected with malaria parasites including Plasmodium falciparum (n = 71, 2.06 %), Plasmodium vivax (57, 1.65 %), P. falciparum-P. vivax (2, 0.06 %), Plasmodium ovale (12, 0.35 %), and Plasmodium malariae (1, 0.03 %). A large majority of P. falciparum infections were observed in the Sahelo-Saharan zone. Malaria prevalence (P Mauritania. However, the Sahelian zone had the lowest malaria prevalence, while the Sahelo-Saharan zone had the highest malaria burden. Local changes due to anthropogenic factors (i.e., human migration, urbanization, malaria interventions) should be considered in order to optimize the control strategy.

  11. Malaria treatment services in Nigeria: A review

    Directory of Open Access Journals (Sweden)

    Benjamin SC Uzochukwu

    2010-01-01

    Full Text Available Malaria remains a major Public Health problem in Nigeria and causes death and illness in children and adults, especially pregnant women. Malaria case management remains a vital component of the malaria control strategies. This entails early diagnosis and prompt treatment with effective antimalarial medicines. The objectives of this review is to enable health professionals to understand the magnitude of malaria treatment services in Nigeria, to improve knowledge for rational malaria management within different health system contexts with a view to improving access to malaria treatment. The review therefore looks at the following areas: clinical disease and epidemiology; the burden of malaria in Nigeria; objectives of treatment; antimalarial treatment policy; malaria diagnosis, treatment strategies/ National responses; treatment sources. The review concludes that for improved malaria treatment services in Nigeria, there is an urgent need to develop adequate strategies that will ensure better access to medicines by getting evidence-based and effective medicines to the people who need them, whether by reducing their costs, promoting equity in access, improving their distribution, increasing their efficacy and acceptability, or slowing down the development of antimicrobial resistance.

  12. T-cell responses in malaria

    DEFF Research Database (Denmark)

    Hviid, L; Jakobsen, P H; Abu-Zeid, Y A

    1992-01-01

    Malaria is caused by infection with protozoan parasites of the genus Plasmodium. It remains one of the most severe health problems in tropical regions of the world, and the rapid spread of resistance to drugs and insecticides has stimulated intensive research aimed at the development of a malaria...... vaccine. Despite this, no efficient operative vaccine is currently available. A large amount of information on T-cell responses to malaria antigens has been accumulated, concerning antigens derived from all stages of the parasite life cycle. The present review summarizes some of that information......, and discusses factors affecting the responses of T cells to malaria antigens....

  13. Evidence for novel hepaciviruses in rodents.

    Directory of Open Access Journals (Sweden)

    Jan Felix Drexler

    Full Text Available Hepatitis C virus (HCV is among the most relevant causes of liver cirrhosis and hepatocellular carcinoma. Research is complicated by a lack of accessible small animal models. The systematic investigation of viruses of small mammals could guide efforts to establish such models, while providing insight into viral evolutionary biology. We have assembled the so-far largest collection of small-mammal samples from around the world, qualified to be screened for bloodborne viruses, including sera and organs from 4,770 rodents (41 species; and sera from 2,939 bats (51 species. Three highly divergent rodent hepacivirus clades were detected in 27 (1.8% of 1,465 European bank voles (Myodes glareolus and 10 (1.9% of 518 South African four-striped mice (Rhabdomys pumilio. Bats showed anti-HCV immunoblot reactivities but no virus detection, although the genetic relatedness suggested by the serologic results should have enabled RNA detection using the broadly reactive PCR assays developed for this study. 210 horses and 858 cats and dogs were tested, yielding further horse-associated hepaciviruses but none in dogs or cats. The rodent viruses were equidistant to HCV, exceeding by far the diversity of HCV and the canine/equine hepaciviruses taken together. Five full genomes were sequenced, representing all viral lineages. Salient genome features and distance criteria supported classification of all viruses as hepaciviruses. Quantitative RT-PCR, RNA in-situ hybridisation, and histopathology suggested hepatic tropism with liver inflammation resembling hepatitis C. Recombinant serology for two distinct hepacivirus lineages in 97 bank voles identified seroprevalence rates of 8.3 and 12.4%, respectively. Antibodies in bank vole sera neither cross-reacted with HCV, nor the heterologous bank vole hepacivirus. Co-occurrence of RNA and antibodies was found in 3 of 57 PCR-positive bank vole sera (5.3%. Our data enable new hypotheses regarding HCV evolution and encourage

  14. Rodent models for compulsive alcohol intake.

    Science.gov (United States)

    Hopf, F Woodward; Lesscher, Heidi M B

    2014-05-01

    Continued seeking and drinking of alcohol despite adverse legal, health, economic, and societal consequences is a central hallmark of human alcohol use disorders. This compulsive drive for alcohol, defined by resistance to adverse and deleterious consequences, represents a major challenge when attempting to treat alcoholism clinically. Thus, there has long been interest in developing pre-clinical rodent models for the compulsive drug use that characterizes drug addiction. Here, we review recent studies that have attempted to model compulsive aspects of alcohol and cocaine intake in rodents, and consider technical and conceptual issues that need to be addressed when trying to recapitulate compulsive aspects of human addiction. Aversion-resistant alcohol intake has been examined by pairing intake or seeking with the bitter tastant quinine or with footshock, and exciting recent work has used these models to identify neuroadaptations in the amygdala, cortex, and striatal regions that promote compulsive intake. Thus, rodent models do seem to reflect important aspects of compulsive drives that sustain human addiction, and will likely provide critical insights into the molecular and circuit underpinnings of aversion-resistant intake as well as novel therapeutic interventions for compulsive aspects of addiction.

  15. Spontaneous Type 2 Diabetic Rodent Models

    Science.gov (United States)

    Wang, Yang-wei; Sun, Guang-dong; Sun, Jing; Liu, Shu-jun; Wang, Ji; Xu, Xiao-hong; Miao, Li-ning

    2013-01-01

    Diabetes mellitus, especially type 2 diabetes (T2DM), is one of the most common chronic diseases and continues to increase in numbers with large proportion of health care budget being used. Many animal models have been established in order to investigate the mechanisms and pathophysiologic progress of T2DM and find effective treatments for its complications. On the basis of their strains, features, advantages, and disadvantages, various types of animal models of T2DM can be divided into spontaneously diabetic models, artificially induced diabetic models, and transgenic/knockout diabetic models. Among these models, the spontaneous rodent models are used more frequently because many of them can closely describe the characteristic features of T2DM, especially obesity and insulin resistance. In this paper, we aim to investigate the current available spontaneous rodent models for T2DM with regard to their characteristic features, advantages, and disadvantages, and especially to describe appropriate selection and usefulness of different spontaneous rodent models in testing of various new antidiabetic drugs for the treatment of type 2 diabetes. PMID:23671868

  16. [Malaria in Poland in 2006].

    Science.gov (United States)

    Rosińska, Magdalena

    2008-01-01

    There were 19 cases of malaria meeting European Union case definition for confirmed case registered in Poland in 2006. All of them were imported, including 1 case of relapse: 17 from Africa, 1 from Asia and 1 from Oceania. Species of Plasmodium was determined for 12 cases (68%): P. falciparum in 12 cases and P. vivax in one. There were 15 cases in males and 4 in females. Age at onset ranged from 17 to 59 years and a considerable number of cases occurred in persons 50 years old or older (5.26%). Common reasons for travel to endemic countries included tourism or family visits (10 cases) and professional or missionary travel (5 cases). Only four cases used chemoprophylaxis and the relevant information was missing in 4 cases. In two cases of malaria caused by Pl. falciparum the clinical course was severe and one of them died.

  17. [Malaria in Poland in 2008].

    Science.gov (United States)

    Stepień, Małgorzata

    2010-01-01

    There were 22 malaria cases confirmed according to the European Union cases definition registered in Poland in 2008. All of them were imported, 13 cases (59%) from Africa, 3 from Asia, 5 from Oceania and 1 from South America. Invasion with Plasmodium falciparum was confirmed in 14 cases, P. vivax in 4 cases, mixed invasion in 2 cases and in 2 cases species of Plasmodium was undetermined. There were 13 cases in males and 9 in females. Age at onset ranged from 23 to 58 years and majority of cases were in the age group 25-40. Common reason for travel to endemic countries were tourism (11 cases) and work-related visits (7 cases). Clinical course was severe in 6 cases of P. falciparum malaria and 1 person died because of the disease. Nine cases used chemoprophylaxis during their travel but only one of them appropriately, relevant information was missing in 6 cases.

  18. Malaria in penguins - current perceptions.

    Science.gov (United States)

    Grilo, M L; Vanstreels, R E T; Wallace, R; García-Párraga, D; Braga, É M; Chitty, J; Catão-Dias, J L; Madeira de Carvalho, L M

    2016-08-01

    Avian malaria is a mosquito-borne disease caused by protozoans of the genus Plasmodium, and it is considered one of the most important causes of morbidity and mortality in captive penguins, both in zoological gardens and rehabilitation centres. Penguins are known to be highly susceptible to this disease, and outbreaks have been associated with mortality as high as 50-80% of affected captive populations within a few weeks. The disease has also been reported in wild penguin populations, however, its impacts on the health and fitness of penguins in the wild is not clear. This review provides an overview of the aetiology, life cycle and epidemiology of avian malaria, and provides details on the strategies that can be employed for the diagnostic, treatment and prevention of this disease in captive penguins, discussing possible directions for future research.

  19. Gene targeting in malaria parasites.

    Science.gov (United States)

    Ménard, R; Janse, C

    1997-10-01

    Gene targeting, which permits alteration of a chosen gene in a predetermined way by homologous recombination, is an emerging technology in malaria research. Soon after the development of techniques for stable transformation of red blood cell stages of Plasmodium falciparum and Plasmodium berghei, genes of interest were disrupted in the two species. The main limitations of gene targeting in malaria parasites result from the intracellular growth and slow replication of these parasites. On the other hand, the technology is facilitated by the very high rate of homologous recombination following transformation with targeting constructs (approximately 100%). Here, we describe (i) the vector design and the type of mutation that may be generated in a target locus, (ii) the selection and screening strategies that can be used to identify clones with the desired modification, and (iii) the protocol that was used for disrupting the circumsporozoite protein (CS) and thrombospondin-related anonymous protein (TRAP) genes of P. berghei.

  20. PENENTUAN VEKTOR MALARIA DI FLORES

    Directory of Open Access Journals (Sweden)

    Harijani A. Marwoto

    2012-09-01

    Full Text Available A field study on entomology has been conducted in 6 villages which were located in coastal and in-land areas of Sikka Regency of Central Flores since April 1990 - October 1991. The results of this study showed that the suspected malaria vectors in those areas were An. sundaicus, An. subpictus, An. barbirostris, An. aconitus and An. maculatus. Only 3 species were confirmed as vector using ELISA test, i.e. An. sundaicus, An. barbirostris and An. subpictus with sporosoite rates of 4.2%, 2.1% and 0.1% respectively. An. aconitus, a potential malaria vector in Java and in some onther places was not confirmed as vector in Flores yet. The 3 confirmed vectors were also found positive with sporozoites in West Flores and also found predominant in East Flores.

  1. Deletion of a malaria invasion gene reduces death and anemia, in model hosts.

    Directory of Open Access Journals (Sweden)

    Noé D Gómez

    Full Text Available Malaria parasites induce complex cellular and clinical phenotypes, including anemia, cerebral malaria and death in a wide range of mammalian hosts. Host genes and parasite 'toxins' have been implicated in malarial disease, but the contribution of parasite genes remains to be fully defined. Here we assess disease in BALB/c mice and Wistar rats infected by the rodent malaria parasite Plasmodium berghei with a gene knock out for merozoite surface protein (MSP 7. MSP7 is not essential for infection but in P. falciparum, it enhances erythrocyte invasion by 20%. In vivo, as compared to wild type, the P. berghei Δmsp7 mutant is associated with an abrogation of death and a decrease from 3% to 2% in peak, circulating parasitemia. The Δmsp7 mutant is also associated with less anemia and modest increase in the size of follicles in the spleen. Together these data show that deletion of a single parasite invasion ligand modulates blood stage disease, as measured by death and anemia. This work is the first to assess the contribution of a gene present in all plasmodial species in severe disease.

  2. Phenylalanine metabolism regulates reproduction and parasite melanization in the malaria mosquito.

    Science.gov (United States)

    Fuchs, Silke; Behrends, Volker; Bundy, Jacob G; Crisanti, Andrea; Nolan, Tony

    2014-01-01

    The blood meal of the female malaria mosquito is a pre-requisite to egg production and also represents the transmission route for the malaria parasite. The proper and rapid assimilation of proteins and nutrients in the blood meal creates a significant metabolic challenge for the mosquito. To better understand this process we generated a global profile of metabolite changes in response to blood meal of Anopheles gambiae, using Gas Chromatography-Mass Spectrometry (GC-MS). To disrupt a key pathway of amino acid metabolism we silenced the gene phenylalanine hydroxylase (PAH) involved in the conversion of the amino acid phenylalanine into tyrosine. We observed increased levels of phenylalanine and the potentially toxic metabolites phenylpyruvate and phenyllactate as well as a reduction in the amount of tyrosine available for melanin synthesis. This in turn resulted in a significant impairment of the melanotic encapsulation response against the rodent malaria parasite Plasmodium berghei. Furthermore silencing of PAH resulted in a significant impairment of mosquito fertility associated with reduction of laid eggs, retarded vitellogenesis and impaired melanisation of the chorion. Carbidopa, an inhibitor of the downstream enzyme DOPA decarboxylase that coverts DOPA into dopamine, produced similar effects on egg melanization and hatching rate suggesting that egg chorion maturation is mainly regulated via dopamine. This study sheds new light on the role of amino acid metabolism in regulating reproduction and immunity.

  3. Phenylalanine metabolism regulates reproduction and parasite melanization in the malaria mosquito.

    Directory of Open Access Journals (Sweden)

    Silke Fuchs

    Full Text Available The blood meal of the female malaria mosquito is a pre-requisite to egg production and also represents the transmission route for the malaria parasite. The proper and rapid assimilation of proteins and nutrients in the blood meal creates a significant metabolic challenge for the mosquito. To better understand this process we generated a global profile of metabolite changes in response to blood meal of Anopheles gambiae, using Gas Chromatography-Mass Spectrometry (GC-MS. To disrupt a key pathway of amino acid metabolism we silenced the gene phenylalanine hydroxylase (PAH involved in the conversion of the amino acid phenylalanine into tyrosine. We observed increased levels of phenylalanine and the potentially toxic metabolites phenylpyruvate and phenyllactate as well as a reduction in the amount of tyrosine available for melanin synthesis. This in turn resulted in a significant impairment of the melanotic encapsulation response against the rodent malaria parasite Plasmodium berghei. Furthermore silencing of PAH resulted in a significant impairment of mosquito fertility associated with reduction of laid eggs, retarded vitellogenesis and impaired melanisation of the chorion. Carbidopa, an inhibitor of the downstream enzyme DOPA decarboxylase that coverts DOPA into dopamine, produced similar effects on egg melanization and hatching rate suggesting that egg chorion maturation is mainly regulated via dopamine. This study sheds new light on the role of amino acid metabolism in regulating reproduction and immunity.

  4. IDOMAL: an ontology for malaria

    Directory of Open Access Journals (Sweden)

    Topalis Pantelis

    2010-08-01

    Full Text Available Abstract Background Ontologies are rapidly becoming a necessity for the design of efficient information technology tools, especially databases, because they permit the organization of stored data using logical rules and defined terms that are understood by both humans and machines. This has as consequence both an enhanced usage and interoperability of databases and related resources. It is hoped that IDOMAL, the ontology of malaria will prove a valuable instrument when implemented in both malaria research and control measures. Methods The OBOEdit2 software was used for the construction of the ontology. IDOMAL is based on the Basic Formal Ontology (BFO and follows the rules set by the OBO Foundry consortium. Results The first version of the malaria ontology covers both clinical and epidemiological aspects of the disease, as well as disease and vector biology. IDOMAL is meant to later become the nucleation site for a much larger ontology of vector borne diseases, which will itself be an extension of a large ontology of infectious diseases (IDO. The latter is currently being developed in the frame of a large international collaborative effort. Conclusions IDOMAL, already freely available in its first version, will form part of a suite of ontologies that will be used to drive IT tools and databases specifically constructed to help control malaria and, later, other vector-borne diseases. This suite already consists of the ontology described here as well as the one on insecticide resistance that has been available for some time. Additional components are being developed and introduced into IDOMAL.

  5. PENGOBATAN MALARIA DENGAN KOMBINASI ARTEMISININ

    Directory of Open Access Journals (Sweden)

    Emilianan Tjitra

    2012-09-01

    Full Text Available Previous approaches in malaria treatment fail to reduce the morbidity and mortality of malaria. Widespread overuse of antimalarial treatment of clinical malaria may have contributed to increase drug resistance. Moreover, poor compliance or inadequate dosage also selects for parasite resistance. The paradigm of radical treatment using drug combinations may improve the cure rate and compliance, thereby preventing or delaying the emergence of parasites resistant to antimalarial drugs. The ideal combined antimalarial regimen in Indonesia should be safe and tolerated by all age groups, effective and rapidly acting for both P.falciparum and P.vivax malaria, short course, good compliance and acceptable, without resistance and/or cross-resistance or , not widely spread use, cost-effective and affordable. Artemisinin derivatives are the best partner drug for combination, with advantages that include: well absorbed, safe and well tolerated, rapidly converted to active metabolite, having very short half-life, broad specificity of action, and extremely potent. Current artemisinin-based combinations which are suitable for Indonesia include: amodiaquine plus artesunate given as single daily dose for 3 days (AQ3+ATS3, mefloquine plus artesunate given as single daily dose for 3 days (MQ3+ATS3, lumefantrine/benflumetol plus artemether given as twice daily dose for 3 days (COARTEMETHER, piperaquine plus dihydroartemisinin given as single daily dose for 2-3 days (PPQ2-3+DHA2-3, and piperaquine plus artemisinin given as single daily dose for 2 days (PPQ2+ATM2. Given the imbalance between rapid development of parasite resistance and slow availability of new effective antimalarial drugs, research and development of antimalarial drugs must be encouraged.

  6. Nifs and Sufs in malaria.

    Science.gov (United States)

    Ellis, K E; Clough, B; Saldanha, J W; Wilson, R J

    2001-09-01

    This review assembles data from three bodies of literature (bacterial genetics, plastid biogenesis and parasitology) that seldom have much direct cross-talk. After overcoming terminological complications to sort out microbial nifS from sufS genes, we connect a bacterial operon, recently found to be involved in iron metabolism, the formation of [Fe-S] clusters and oxidative stress to a potentially important gene (sufB) carried on the degenerate plastid genome of malaria and related parasites.

  7. PENGOBATAN MALARIA DENGAN KOMBINASI ARTEMISININ

    Directory of Open Access Journals (Sweden)

    Emilianan Tjitra

    2012-09-01

    Full Text Available Previous approaches in malaria treatment fail to reduce the morbidity and mortality of malaria. Widespread overuse of antimalarial treatment of clinical malaria may have contributed to increase drug resistance. Moreover, poor compliance or inadequate dosage also selects for parasite resistance. The paradigm of radical treatment using drug combinations may improve the cure rate and compliance, thereby preventing or delaying the emergence of parasites resistant to antimalarial drugs. The ideal combined antimalarial regimen in Indonesia should be safe and tolerated by all age groups, effective and rapidly acting for both P.falciparum and P.vivax malaria, short course, good compliance and acceptable, without resistance and/or cross-resistance or , not widely spread use, cost-effective and affordable. Artemisinin derivatives are the best partner drug for combination, with advantages that include: well absorbed, safe and well tolerated, rapidly converted to active metabolite, having very short half-life, broad specificity of action, and extremely potent. Current artemisinin-based combinations which are suitable for Indonesia include: amodiaquine plus artesunate given as single daily dose for 3 days (AQ3+ATS3, mefloquine plus artesunate given as single daily dose for 3 days (MQ3+ATS3, lumefantrine/benflumetol plus artemether given as twice daily dose for 3 days (COARTEMETHER, piperaquine plus dihydroartemisinin given as single daily dose for 2-3 days (PPQ2-3+DHA2-3, and piperaquine plus artemisinin given as single daily dose for 2 days (PPQ2+ATM2. Given the imbalance between rapid development of parasite resistance and slow availability of new effective antimalarial drugs, research and development of antimalarial drugs must be encouraged.

  8. The Malaria Problem: short communication

    Directory of Open Access Journals (Sweden)

    Charles Ebikeme

    2010-09-01

    Full Text Available Malaria is the world's most prevalent infectious disease, a major cause of mortality, and a barrier to social and economic development and growth in many countries throughout the world. Antimalarials represent an important part of strategy to curbing this debilitating disease. The spread of drug resistance is becoming increasingly important. To date, parasite resistance to all but one case of antimalarials exists in most endemic countries. Meaning, new drug to combat the disease are a priority.

  9. The efficiency of malaria chemoprophylaxis

    Directory of Open Access Journals (Sweden)

    Vasiliki Pappa

    2008-07-01

    Full Text Available Introduction: Malaria is a highly contagious disease. According to WHO, malaria cases are expected to increase due to climate changes. Despite the eradication efforts, malaria still remains one of the most significant causes of morbidity and mortality in tropical and subtropical regions. Many different antimalarial regimens are used , however resistance is emerging to many of themPurpose: This critical review was conducted, in order to respond to the following questions. A Which antimalarial regimen is most effective? B Which regimen is the safest for travelers in endemic regions? C Which regimen is best tolerated?Methodology: The literature research was conducted through the Internet. The Medline and Cinahl databases were used, as well as the search engines google, altavista and lycos. The research included articles that described clinical trials. The material was selected based on the aforementioned research questions and the chronological time limits.Results: Atovaquone/proguanil, tafenoquine, primaquine were the most effective regimens. Tafenoquine, as well as, primaquine have been related to hemolytic events in individuals with G6PD deficiency, gastrointestinal disorders, backache and flue-like syndrome. Doxycycline and mefloquine were related to gastrointestinal and neurological disorders. Those were the less tolerated regimens.Conclusions: Atovaquone/proguanil, tafenoquine, primaquine were the most effective regimens. As far as safety is concerned, tafenoquine and primaquine should not be prescribed to individuals with G6PD deficiency. All the regimens were considered well tolerated, however, in doxycycline and mefloquine trials were the most withdrawals due to adverse effects.

  10. [Microbiological diagnosis of imported malaria].

    Science.gov (United States)

    Torrús, Diego; Carranza, Cristina; Manuel Ramos, José; Carlos Rodríguez, Juan; Rubio, José Miguel; Subirats, Mercedes; Ta-Tang, Thuy-Huong

    2015-07-01

    Current diagnosis of malaria is based on the combined and sequential use of rapid antigen detection tests (RDT) of Plasmodium and subsequent visualization of the parasite stained with Giemsa solution in a thin and thick blood smears. If an expert microscopist is not available, should always be a sensitive RDT to rule out infection by Plasmodium falciparum, output the result immediately and prepare thick smears (air dried) and thin extensions (fixed with methanol) for subsequent staining and review by an expert microscopist. The RDT should be used as an initial screening test, but should not replace microscopy techniques, which should be done in parallel. The diagnosis of malaria should be performed immediately after clinical suspicion. The delay in laboratory diagnosis (greater than 3 hours) should not prevent the initiation of empirical antimalarial treatment if the probability of malaria is high. If the first microscopic examination and RDT are negative, they must be repeated daily in patients with high suspicion. If suspicion remains after three negative results must be sought the opinion of an tropical diseases expert. Genomic amplification methods (PCR) are useful as confirmation of microscopic diagnosis, to characterize mixed infections undetectable by other methods, and to diagnose asymptomatic infections with submicroscopic parasitaemia.

  11. Suppression of parasite-specific response in Plasmodium falciparum malaria. A longitudinal study of blood mononuclear cell proliferation and subset composition

    DEFF Research Database (Denmark)

    Theander, T G; Bygbjerg, I C; Andersen, B J

    1986-01-01

    -specific proliferative response. The subset composition of BMNC isolated from non-immune patients was studied in a FACS analyser. The mean cell volumes of both Leu 2+ and Leu 3+ cells were increased during the acute phase of the infection, indicating that malaria infection results in activation of both T-helper and T......The present longitudinal study was designed to characterize immunosuppression during acute Plasmodium falciparum infection, during the treatment and up to 1 month after the acute stage. The proliferative responses of blood mononuclear cells (BMNC) isolated from non-immune and semi-immune malaria......-suppressor cells. There was no overall reduction of the response to mitogens on day 0. However, 3 days after initiation of the treatment the mitogen response was decreased. This finding indicates that it is important to distinguish between the effects of malaria infection and of drug treatment....

  12. Automated detection of malaria pigment: feasibility for malaria diagnosing in an area with seasonal malaria in northern Namibia

    NARCIS (Netherlands)

    A.J. de Langen; J. van Dillen; P. Witte; S. Mucheto; N. Nagelkerke; P. Kager

    2006-01-01

    OBJECTIVE To evaluate the feasibility of automated malaria detection with the Cell-Dyn (R) 3700 (Abbott Diagnostics, Santa Clara, CA, USA) haematology analyser for diagnosing malaria in northern Namibia. METHODS From April to June 2003, all patients with a positive blood smear result and a subset of

  13. Determinan Kejadian Malaria di Wilayah Endemis

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    Hamzah Hasyim

    2014-02-01

    Full Text Available Kabupaten Lahat adalah salah satu wilayah endemis malaria di Sumatera Selatan dengan prevalensi 16,4% dan Annual Malaria Incidence 22,08. Tujuan penelitian ini untuk mengetahui faktor risiko lingkungan dengan kejadian malaria. Faktor risiko lingkungan genangan air (breeding place berhubungan dengan kejadian malaria dengan nilai p= 0,000. Analisis multivariat menemukan determinan utama kejadian malaria adalah breeding place di sekitar rumah responden dengan odds ratio (OR = 5,034 dan 95% CI = 2,65 _ 9,56. Responden yang tinggal di sekitar breeding place berisiko 5,03 kali lebih besar untuk menderita malaria dibandingkan dengan responden yang di sekitar rumah tidak terdapat breeding place setelah dikontrol variabel jarak rumah ke breeding place, ventilasi rumah, penggunaan kelambu, penggunaan obat anti nyamuk, dan kebiasaan keluar rumah pada malam hari. Lahat district is one of the malaria endemic area in South Sumatra Province with a prevalence of 16.4% and Annual Malaria Incidence of 22.08. The case control reports were carried out of 240 respondents. This study aimed to understand the relationship among of environmental risk factors with the incidence of malaria. After primary data collection followed by processing and data analysis in a multimedia laboratory. There was association between breeding place and malaria cases (p value= 0.000. The results of multivariate analysis of variables revealed the determinant risk was breeding place, with OR = 5.034 and CI 95%= 2.65 _ 9.56. Respondents who live around the breeding place has 5.034 times chance of affected malaria compared with respondents around the house there are no breeding place after the controlled distance to the breeding place house, use of mosquito nets, use of anti-mosquito, and habits out of the house at night variables.

  14. Climate, environment and transmission of malaria.

    Science.gov (United States)

    Rossati, Antonella; Bargiacchi, Olivia; Kroumova, Vesselina; Zaramella, Marco; Caputo, Annamaria; Garavelli, Pietro Luigi

    2016-06-01

    Malaria, the most common parasitic disease in the world, is transmitted to the human host by mosquitoes of the genus Anopheles. The transmission of malaria requires the interaction between the host, the vector and the parasite.The four species of parasites responsible for human malaria are Plasmodium falciparum, Plasmodium ovale, Plasmodium malariae and Plasmodium vivax. Occasionally humans can be infected by several simian species, like Plasmodium knowlesi, recognised as a major cause of human malaria in South-East Asia since 2004. While P. falciparum is responsible for most malaria cases, about 8% of estimated cases globally are caused by P. vivax. The different Plasmodia are not uniformly distributed although there are areas of species overlap. The life cycle of all species of human malaria parasites is characterised by an exogenous sexual phase in which multiplication occurs in several species of Anopheles mosquitoes, and an endogenous asexual phase in the vertebrate host. The time span required for mature oocyst development in the salivary glands is quite variable (7-30 days), characteristic of each species and influenced by ambient temperature. The vector Anopheles includes 465 formally recognised species. Approximately 70 of these species have the capacity to transmit Plasmodium spp. to humans and 41 are considered as dominant vector capable of transmitting malaria. The intensity of transmission is dependent on the vectorial capacity and competence of local mosquitoes. An efficient system for malaria transmission needs strong interaction between humans, the ecosystem and infected vectors. Global warming induced by human activities has increased the risk of vector-borne diseases such as malaria. Recent decades have witnessed changes in the ecosystem and climate without precedent in human history although the emphasis in the role of temperature on the epidemiology of malaria has given way to predisposing conditions such as ecosystem changes, political

  15. Climate change and the global malaria recession.

    Science.gov (United States)

    Gething, Peter W; Smith, David L; Patil, Anand P; Tatem, Andrew J; Snow, Robert W; Hay, Simon I

    2010-05-20

    The current and potential future impact of climate change on malaria is of major public health interest. The proposed effects of rising global temperatures on the future spread and intensification of the disease, and on existing malaria morbidity and mortality rates, substantively influence global health policy. The contemporary spatial limits of Plasmodium falciparum malaria and its endemicity within this range, when compared with comparable historical maps, offer unique insights into the changing global epidemiology of malaria over the last century. It has long been known that the range of malaria has contracted through a century of economic development and disease control. Here, for the first time, we quantify this contraction and the global decreases in malaria endemicity since approximately 1900. We compare the magnitude of these changes to the size of effects on malaria endemicity proposed under future climate scenarios and associated with widely used public health interventions. Our findings have two key and often ignored implications with respect to climate change and malaria. First, widespread claims that rising mean temperatures have already led to increases in worldwide malaria morbidity and mortality are largely at odds with observed decreasing global trends in both its endemicity and geographic extent. Second, the proposed future effects of rising temperatures on endemicity are at least one order of magnitude smaller than changes observed since about 1900 and up to two orders of magnitude smaller than those that can be achieved by the effective scale-up of key control measures. Predictions of an intensification of malaria in a warmer world, based on extrapolated empirical relationships or biological mechanisms, must be set against a context of a century of warming that has seen marked global declines in the disease and a substantial weakening of the global correlation between malaria endemicity and climate.

  16. Scale-up of community-based malaria control can be achieved without degrading community health workers' service quality: the Village Malaria Worker project in Cambodia.

    Science.gov (United States)

    Yasuoka, Junko; Poudel, Krishna C; Ly, Po; Nguon, Chea; Socheat, Duong; Jimba, Masamine

    2012-01-04

    Malaria control has been scaled up in many developing countries in their efforts to achieve the Millennium Development Goals. Cambodia recently scaled up their Village Malaria Worker (VMW) project by substantially increasing the number of VMWs and expanding the project's health services to include treatment of fever, diarrhoea, and Acute Respiratory Infections (ARI) in children under five. This study examined if the scale-up interfered with VMWs' service quality, actions, and knowledge of malaria control, and analysed VMWs' overall achievements and perceptions of the newly added health services. Structured interviews were conducted pre scale-up in February-March 2008 with 251 VMWs and post scale-up in July-August 2010 with 252 VMWs. Comparing the pre and post scale-up survey results (n = 195), changes were examined in terms of VMWs' 1) service quality, 2) malaria prevention and vector control actions, and 3) knowledge of malaria epidemiology and vector ecology. In addition, VMWs' newly added health services were descriptively analysed based on the post scale-up survey (n = 252). VMWs' service quality and actions significantly improved overall during the scale-up of the VMW project (mean index score: +0.805, p scale-up survey. About 70% of the respondents reported that their health services to control malaria remained the same or that they were more active after the scale-up. Two-thirds (66.3%) had become more enthusiastic about serving as a VMW since the scale-up, and all but one respondent reported being willing to continue the new services. The Cambodian experience clearly demonstrated that a nationwide scale-up of community-based malaria control can be achieved without degrading community health workers' service quality. The government's strategy to expand VMWs' health services, while providing sufficient training to maintain the quality of their original malaria control services, could have contributed to the improvement of VMW's service quality, actions, and

  17. Associations between maternal helminth and malaria infections in pregnancy, and clinical malaria in the offspring

    DEFF Research Database (Denmark)

    Ndibazza, Juliet; Webb, Emily L; Lule, Swaib

    2013-01-01

    Background. Helminth and malaria coinfections are common in the tropics. We investigated the hypothesis that prenatal exposure to these parasites might influence susceptibility to infections such as malaria in childhood.Methods. In a birth cohort of 2,345 mother-child pairs in Uganda, maternal...... helminth and malaria infection status was determined during pregnancy, and childhood malaria episodes recorded from birth to age five years. We examined associations between maternal infections and malaria in the offspring.Results. Common maternal infections were hookworm (45%), Mansonella perstans (21......%), Schistosoma mansoni (18%), and Plasmodium falciparum (11%). At age 5 years, 69% of the children were still under follow-up. The incidence of malaria was 34 episodes per 100 child-years, and the mean prevalence of asymptomatic malaria at annual visits was 5.4%. Maternal hookworm and M. perstans infections were...

  18. A novel ENU-induced ankyrin-1 mutation impairs parasite invasion and increases erythrocyte clearance during malaria infection in mice

    Science.gov (United States)

    Huang, Hong Ming; Bauer, Denis C.; Lelliott, Patrick M.; Greth, Andreas; McMorran, Brendan J.; Foote, Simon J.; Burgio, Gaetan

    2016-01-01

    Genetic defects in various red blood cell (RBC) cytoskeletal proteins have been long associated with changes in susceptibility towards malaria infection. In particular, while ankyrin (Ank-1) mutations account for approximately 50% of hereditary spherocytosis (HS) cases, an association with malaria is not well-established, and conflicting evidence has been reported. We describe a novel N-ethyl-N-nitrosourea (ENU)-induced ankyrin mutation MRI61689 that gives rise to two different ankyrin transcripts: one with an introduced splice acceptor site resulting a frameshift, the other with a skipped exon. Ank-1(MRI61689/+) mice exhibit an HS-like phenotype including reduction in mean corpuscular volume (MCV), increased osmotic fragility and reduced RBC deformability. They were also found to be resistant to rodent malaria Plasmodium chabaudi infection. Parasites in Ank-1(MRI61689/+) erythrocytes grew normally, but red cells showed resistance to merozoite invasion. Uninfected Ank-1(MRI61689/+) erythrocytes were also more likely to be cleared from circulation during infection; the “bystander effect”. This increased clearance is a novel resistance mechanism which was not observed in previous ankyrin mouse models. We propose that this bystander effect is due to reduced deformability of Ank-1(MRI61689/+) erythrocytes. This paper highlights the complex roles ankyrin plays in mediating malaria resistance. PMID:27848995

  19. Interruption of the blood-stage cycle of the malaria parasite, Plasmodium chabaudi, by protein tyrosine kinase inhibitors

    Directory of Open Access Journals (Sweden)

    M.L. Gazarini

    2003-11-01

    Full Text Available Malaria is a devastating disease caused by a unicellular protozoan, Plasmodium, which affects 3.7 million people every year. Resistance of the parasite to classical treatments such as chloroquine requires the development of new drugs. To gain insight into the mechanisms that control Plasmodium cell cycle, we have examined the effects of kinase inhibitors on the blood-stage cycle of the rodent malaria parasite, Plasmodium chabaudi. In vitro incubation of red blood cells for 17 h at 37ºC with the inhibitors led to a decrease in the percent of infected cells, compared to control treatment, as follows: genistein (200 µM - 75%, staurosporine (1 µM - 58%, R03 (1 µM - 75%, and tyrphostins B44 (100 µM - 66% and B46 (100 µM - 68%. All these treatments were shown to retard or prevent maturation of the intraerythrocytic parasites. The diverse concentration ranges at which these inhibitors exert their effects give a clue as to the types of signals that initiate the transitions between the different developmental stages of the parasite. The present data support our hypothesis that the maturation of the intraerythrocytic cycle of malaria parasites requires phosphorylation. In this respect, we have recently reported a high Ca2+ microenvironment surrounding the parasite within red blood cells. Several kinase activities are modulated by Ca2+. The molecular identification of the targets of these kinases could provide new strategies against malaria.

  20. The Puf-family RNA-binding protein Puf2 controls sporozoite conversion to liver stages in the malaria parasite.

    Directory of Open Access Journals (Sweden)

    Katja Müller

    Full Text Available Malaria is a vector-borne infectious disease caused by unicellular, obligate intracellular parasites of the genus Plasmodium. During host switch the malaria parasite employs specialized latent stages that colonize the new host environment. Previous work has established that gametocytes, sexually differentiated stages that are taken up by the mosquito vector, control expression of genes required for mosquito colonization by translational repression. Sexual parasite development is controlled by a DEAD-box RNA helicase of the DDX6 family, termed DOZI. Latency of sporozoites, the transmission stage injected during an infectious blood meal, is controlled by the eIF2alpha kinase IK2, a general inhibitor of protein synthesis. Whether RNA-binding proteins participate in translational regulation in sporozoites remains to be studied. Here, we investigated the roles of two RNA-binding proteins of the Puf-family, Plasmodium Puf1 and Puf2, during sporozoite stage conversion. Our data reveal that, in the rodent malaria parasite P. berghei, Puf2 participates in the regulation of IK2 and inhibits premature sporozoite transformation. Inside mosquito salivary glands puf2⁻ sporozoites transform over time to round forms resembling early intra-hepatic stages. As a result, mutant parasites display strong defects in initiating a malaria infection. In contrast, Puf1 is dispensable in vivo throughout the entire Plasmodium life cycle. Our findings support the notion of a central role for Puf2 in parasite latency during switch between the insect and mammalian hosts.