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Sample records for plasmodium berghei malaria

  1. 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...

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

    Science.gov (United States)

    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.

  3. Antimalarial properties of Artemisia vulgaris L. ethanolic leaf extract in a Plasmodium berghei murine malaria model

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    Gayan S. Bamunuarachchi

    2013-12-01

    Full Text Available Background & objectives: Artemisinin isolated from Artemisia annua is the most potent antimalarial drug against chloroquine-resistant Plasmodium falciparum malaria. Artemisia vulgaris, an invasive weed, is the only Artemisia species available in Sri Lanka. A pilot study was undertaken to investigate the antiparasitic activity of an A. vulgaris ethanolic leaf extract (AVELE in a P. berghei ANKA murine malaria model that elicits pathogenesis similar to falciparum malaria. Methods: A 4-day suppressive and the curative assays determined the antiparasitic activity of AVELE using four doses (250, 500, 750 and 1000 mg/kg, Coartem® as the positive control and 5% ethanol as the negative control in male ICR mice infected with P. berghei. Results: The 500, 750 and 1000 mg/kg doses of AVELE significantly (p ≤0.01 inhibited parasitaemia by 79.3, 79.6 and 87.3% respectively, in the 4-day suppressive assay, but not in the curative assay. Chronic administration of the high dose of AVELE ruled out overt signs of toxicity and stress as well as hepatotoxicity, renotoxicity and haematotoxicity. Interpretation & conclusion: The oral administration of a crude ethonolic leaf extract of A. vulgaris is non-toxic and possesses potent antimalarial properties in terms of antiparasitic activity.

  4. Cytokine response to pregnancy-associated recrudescence of Plasmodium berghei infection in mice with pre-existing immunity to malaria

    DEFF Research Database (Denmark)

    Megnekou, Rosette; Staalsoe, Trine; Hviid, Lars

    2013-01-01

    During childhood, residents of areas with stable transmission of Plasmodium falciparum parasites acquire substantial protective immunity to malaria, and adults therefore rarely experience clinical disease episodes. However, susceptibility to infection reappears in pregnant women, particularly...... primigravidae. This is due to appearance of antigenic parasite variants that are restricted to pregnancy. Variant-specific immunity also governs pregnancy-associated recrudescence of Plasmodium berghei infection in pregnant mice. Pregnancy-related changes in the plasma cytokine levels of mice with immunity...

  5. 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.

  6. Plasmodium Berghei ANKA Infection in ICR Mice as a Model of Cerebral Malaria

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    F Othman

    2012-12-01

    Full Text Available Background: Animal models with various combination of host-parasite have long been employed to study malaria pathogenesis. Here, we describe the combination of Plasmodium berghei ANKA infec­tion in inbred ICR mice as a model of cerebral malaria (CM.Methods: Infection in mice was initiated by intraperitoneal injection of 2 x 107 (0.2ml parasitized red blood cells (PRBCs.Results: This model can produce a severe degree of infection presented by the high degree of parasitae­mia followed by death 6-7 days post infection. Severe anemia, splenomegaly, hepatomegaly and discolourations of major organs were observed. Histopathological findings revealed several impor­tant features mimicking human CM including, microvascular sequestration of PRBCs in major organs, particularly in the brain, hypertrophy and hyperplasia of the kupffer cells in the liver, pulmo­nary edema and hyaline membrane formation in the lungs and haemorrhages in the kidney’s medulla and cortex. Proinflammatory cytokines TNFα, IFNγ, IL-1, IL-6 and IL-18, and anti-inflammatory cytokine IL-10 were all found to be elevated in the plasma of infected mice.Conclusion: This model can reproduce many of the important features of CM and therefore can be used as a tool to advance our understanding of the disease pathogenesis.

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

    Science.gov (United States)

    Matsuoka, Hiroyuki; Tomita, Hiroyuki; Hattori, Ryuta; Arai, Meiji; Hirai, Makoto

    2015-03-01

    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 previous TG parasites. The estimated number of injected sporozoites by mosquitoes was between 34 and 775 (median 80). Since luciferase activity diminished immediately after the death of the parasites, luciferase activity could be an indicator of the existence of live parasites. Our results indicated that sporozoites survived at the probed site for more than 42 hours. We also detected sporozoites in the liver within 15 min of the intravenous injection. Bioluminescence was not observed in the lung, kidney or spleen. We confirmed the observation that the liver was the first organ in which malaria parasites entered and increased in number.

  8. Influence of antimalarial treatment on acquisition of immunity in Plasmodium berghei NK65 malaria.

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    Long, Ton That Ai; Nakazawa, Shusuke; Huaman, Maria Cecilia; Kanbara, Hiroji

    2002-07-01

    Antimalarial treatments during primary Plasmodium berghei NK65 infection in BALB/c mice influenced the acquisition of protective immunity against reinfection. Among subcurative treatments, lower doses better enable mice to acquire protective immunity than do higher doses. Eradication of parasites from the start of infection did not promote protective immunity.

  9. Pregnancy outcome and placenta pathology in Plasmodium berghei ANKA infected mice reproduce the pathogenesis of severe malaria in pregnant women.

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    Rita Neres

    Full Text Available Pregnancy-associated malaria (PAM is expressed in a range of clinical complications that include increased disease severity in pregnant women, decreased fetal viability, intra-uterine growth retardation, low birth weight and infant mortality. The physiopathology of malaria in pregnancy is difficult to scrutinize and attempts were made in the past to use animal models for pregnancy malaria studies. Here, we describe a comprehensive mouse experimental model that recapitulates many of the pathological and clinical features typical of human severe malaria in pregnancy. We used P. berghei ANKA-GFP infection during pregnancy to evoke a prominent inflammatory response in the placenta that entails CD11b mononuclear infiltration, up-regulation of MIP-1 alpha chemokine and is associated with marked reduction of placental vascular spaces. Placenta pathology was associated with decreased fetal viability, intra-uterine growth retardation, gross post-natal growth impairment and increased disease severity in pregnant females. Moreover, we provide evidence that CSA and HA, known to mediate P. falciparum adhesion to human placenta, are also involved in mouse placental malaria infection. We propose that reduction of maternal blood flow in the placenta is a key pathogenic factor in murine pregnancy malaria and we hypothesize that exacerbated innate inflammatory responses to Plasmodium infected red blood cells trigger severe placenta pathology. This experimental model provides an opportunity to identify cell and molecular components of severe PAM pathogenesis and to investigate the inflammatory response that leads to the observed fetal and placental blood circulation abnormalities.

  10. Type I interferons contribute to experimental cerebral malaria development in response to sporozoite or blood-stage Plasmodium berghei ANKA.

    Science.gov (United States)

    Palomo, Jennifer; Fauconnier, Mathilde; Coquard, Laurie; Gilles, Maïlys; Meme, Sandra; Szeremeta, Frederic; Fick, Lizette; Franetich, Jean-François; Jacobs, Muazzam; Togbe, Dieudonnée; Beloeil, Jean-Claude; Mazier, Dominique; Ryffel, Bernhard; Quesniaux, Valerie F J

    2013-10-01

    Cerebral malaria is a severe complication of Plasmodium falciparum infection. Although T-cell activation and type II IFN-γ are required for Plasmodium berghei ANKA (PbA)-induced murine experimental cerebral malaria (ECM), the role of type I IFN-α/β in ECM development remains unclear. Here, we address the role of the IFN-α/β pathway in ECM devel-opment in response to hepatic or blood-stage PbA infection, using mice deficient for types I or II IFN receptors. While IFN-γR1⁻/⁻ mice were fully resistant, IFNAR1⁻/⁻ mice showed delayed and partial protection to ECM after PbA infection. ECM resistance in IFN-γR1⁻/⁻ mice correlated with unaltered cerebral microcirculation and absence of ischemia, while WT and IFNAR1⁻/⁻ mice developed distinct microvascular pathologies. ECM resistance appeared to be independent of parasitemia. Instead, key mediators of ECM were attenuated in the absence of IFNAR1, including PbA-induced brain sequestration of CXCR3⁺-activated CD8⁺ T cells. This was associated with reduced expression of Granzyme B, IFN-γ, IL-12Rβ2, and T-cell-attracting chemokines CXCL9 and CXCL10 in IFNAR1⁻/⁻ mice, more so in the absence of IFN-γR1. Therefore, the type I IFN-α/β receptor pathway contributes to brain T-cell responses and microvascular pathology, although it is not as essential as IFN-γ for the development of cerebral malaria upon hepatic or blood-stage PbA infection. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Variant-specific immunity to Plasmodium berghei in pregnant mice

    DEFF Research Database (Denmark)

    Megnekou, Rosette; Hviid, Lars; Staalsoe, Trine

    2009-01-01

    to the P. falciparum erythrocyte membrane protein 1 adhesins, which are of key importance in P. falciparum malaria. The study of P. berghei malaria in pregnant, immune mice can be used to gain significant new insights regarding malaria pathogenesis and immunity in general and regarding PAM in particular.......We have investigated the immunological basis of pregnancy-related Plasmodium berghei recrudescence in immune mice with substantial preexisting immunity. Specifically, we examined the relevance of this experimental model to the study of pregnancy-associated malaria (PAM) caused by P. falciparum...

  12. The novel oxygenated chalcone, 2,4-dimethoxy-4'-butoxychalcone, exhibits potent activity against human malaria parasite Plasmodium falciparum in vitro and rodent parasites Plasmodium berghei and Plasmodium yoelii in vivo

    DEFF Research Database (Denmark)

    Chen, M; Brøgger Christensen, S; Zhai, L

    1997-01-01

    growth of both a chloroquine-susceptible (3D7) and a chloroquine-resistant (Dd2) strain of Plasmodium falciparum in a [3H]hypoxanthine uptake assay. The in vivo activity of 2,4mbc was tested in mice infected with Plasmodium berghei or Plasmodium yoelii and in rats infected with P. berghei. 2,4mbc...

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

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    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.

  14. In vivo and in vitro effectiveness of Azadirachta indica-synthesized silver nanocrystals against Plasmodium berghei and Plasmodium falciparum, and their potential against malaria mosquitoes.

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    Murugan, Kadarkarai; Panneerselvam, Chellasamy; Samidoss, Christina Mary; Madhiyazhagan, Pari; Suresh, Udaiyan; Roni, Mathath; Chandramohan, Balamurugan; Subramaniam, Jayapal; Dinesh, Devakumar; Rajaganesh, Rajapandian; Paulpandi, Manickam; Wei, Hui; Aziz, Al Thabiani; Alsalhi, Mohamad Saleh; Devanesan, Sandhanasamy; Nicoletti, Marcello; Pavela, Roman; Canale, Angelo; Benelli, Giovanni

    2016-06-01

    Malaria transmission is a serious emergence in urban and semiurban areas worldwide, becoming a major international public health concern. Malaria is transmitted through the bites of Anopheles mosquitoes. The extensive employ of synthetic pesticides leads to negative effects on human health and the environment. Recently, plant-synthesized nanoparticles have been proposed as highly effective mosquitocides. In this research, we synthesized silver nanoparticles (AgNP) using the Azadirachta indica seed kernel extract as reducing and stabilizing agent. AgNP were characterized by UV-vis spectrophotometry, SEM, EDX, XRD and FTIR spectroscopy. The A. indica seed kernel extract was toxic against Anopheles stephensi larvae and pupae, LC50 were 232.8ppm (larva I), 260.6ppm (II), 290.3ppm (III), 323.4ppm (IV), and 348.4ppm (pupa). AgNP LC50 were 3.9ppm (I), 4.9ppm (II), 5.6ppm (III), 6.5ppm (IV), and 8.2ppm (pupa). The antiplasmodial activity of A. indica seed kernel extract and AgNP was evaluated against CQ-resistant (CQ-r) and CQ-sensitive (CQ-s) strains of Plasmodium falciparum. IC50 of A. indica seed kernel extract were 63.18μg/ml (CQ-s) and 69.24μg/ml (CQ-r). A. indica seed kernel-synthesized AgNP achieved IC50, of 82.41μg/ml (CQ-s) and 86.12μg/ml (CQ-r). However, in vivo anti-plasmodial experiments conducted on Plasmodium berghei infecting albino mice showed moderate activity of the A. indica extract and AgNP. Overall, this study showed that the A. indica-mediated fabrication of AgNP is of interest for a wide array of purposes, ranging from IPM of mosquito vectors to the development of novel and cheap antimalarial drugs.

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

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    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

  16. Protection from experimental cerebral malaria with a single dose of radiation-attenuated, blood-stage Plasmodium berghei parasites.

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    Noel J Gerald

    Full Text Available BACKGROUND: Whole malaria parasites are highly effective in inducing immunity against malaria. Due to the limited success of subunit based vaccines in clinical studies, there has been a renewed interest in whole parasite-based malaria vaccines. Apart from attenuated sporozoites, there have also been efforts to use live asexual stage parasites as vaccine immunogens. METHODOLOGY AND RESULTS: We used radiation exposure to attenuate the highly virulent asexual blood stages of the murine malaria parasite P. berghei to a non-replicable, avirulent form. We tested the ability of the attenuated blood stage parasites to induce immunity to parasitemia and the symptoms of severe malaria disease. Depending on the mouse genetic background, a single high dose immunization without adjuvant protected mice from parasitemia and severe disease (CD1 mice or from experimental cerebral malaria (ECM (C57BL/6 mice. A low dose immunization did not protect against parasitemia or severe disease in either model after one or two immunizations. The protection from ECM was associated with a parasite specific antibody response and also with a lower level of splenic parasite-specific IFN-γ production, which is a mediator of ECM pathology in C57BL/6 mice. Surprisingly, there was no difference in the sequestration of CD8+ T cells and CD45+ CD11b+ macrophages in the brains of immunized, ECM-protected mice. CONCLUSIONS: This report further demonstrates the effectiveness of a whole parasite blood-stage vaccine in inducing immunity to malaria and explicitly demonstrates its effectiveness against ECM, the most pathogenic consequence of malaria infection. This experimental model will be important to explore the formulation of whole parasite blood-stage vaccines against malaria and to investigate the immune mechanisms that mediate protection against parasitemia and cerebral malaria.

  17. Identification of Pfdhfr mutant variants in Plasmodium berghei model

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    Chairat Uthaipibull

    2011-12-01

    Full Text Available Parasite resistance to antimalarials is a major burden in controlling malaria disease. Genetic mutations within the parasites are found to be the factor in conferring resistance to drugs. In this study, the power of random mutant library and transgenic parasite systems were employed to identify mutations on the antimalarial drug target, viz. Plasmodium falciparum dihydrofolate reductase (DHFR, which could contribute to resistance, and to elucidate the functionality of resistant mutant parasites in P. berghei. Using the moderate drug-resistant PfdhfrS108N gene as template, we generated a library of Pfdhfr mutants by error-prone PCR followed by transfection and selection in P. berghei. Two clones of transgenic P. berghei expressing PfDHFR of interest due to the position of mutations, i.e. PbPfDHFR3m1 (M55I+S108N+S189C and PbPfDHFR3m2 (C50Y+S108N+F116S, were selected for drug sensitivity test. Although these transgenic parasite clones showed similar reproducibility with the parental transgenic P. berghei, expressing PfDHFR with mutation at S108N (PbPfS108N in response to antifolate pyrimethamine, this study reconfirms that this P. berghei model is effective in predicting the evolution of Pfdhfr mutations in vivo. This approach can be applied during the development of new antifolates with better effective properties against drug resistant parasites.

  18. Dietary supplementation of chloroquine with nigella sativa seed and oil extracts in the treatment of malaria induced in mice with plasmodium berghei

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    Promise Madu Emeka

    2014-01-01

    Full Text Available Background: The aim of the study was to investigate the effects of dietary combination of Nigella sativa seed and oil extracts with chloroquine (CQ, and how these combinations enhance CQ efficacy in mice infected with Plasmodium berghei and their survival rates. Materials and Methods: Chloroquine sensitive P. berghei, NK65 strain was used for the study. This was passaged intraperitoneally into albino mice with a 0.2ml standard inoculum consisting of 10 6 parasitized erythrocyte suspension in phosphate buffer solution (PBS. Parasitaemia was ascertained by microscopical examination of blood films under oil immersion at X100 magnification. Results: Nigella sativa seed in feed (NSSF, NSSF + CQ on day 4, produced 86.1% and 86.0% suppression respectively, while Nigella sativa oil extract in feed (NSOF and in combination with CQ had 86.0% and 99.9% suppression respectively. The degree of suppression with the combination was significantly higher compared to CQ alone (P < 0.001 (36.1%. Complete parasitaemia clearance was obtained on the 20 th and 15 th day of treatment for NSSF, NSSF + CQ respectively, while that for NSOF and NSOF + CQ was on days 26 and 12 respectively. For CQ parasite clearance was 12 days with treatment. Also, the combinastion of 10 mg/kg Nigella sativa oil treatment injected intraperitoneally with oral CQ produced very significant parasite suppression (P < 0.0001 (93%. Survival rate in NSSF and NSOF and in combination with CQ groups was 100 and 60.0% for CQ alone. Conclusion : sThis study shows that the use of Nigella sativa seed and oil extract as dietary supplements in combination with CQ has a potential in enhancing the efficacy of CQ and could be of benefit in management of malaria.

  19. Dietary supplementation of chloroquine with nigella sativa seed and oil extracts in the treatment of malaria induced in mice with plasmodium berghei

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    Emeka, Promise Madu; Badger-Emeka, Lorina Ineta; Eneh, Chiamaka Maryann; Khan, Tahir Mahmood

    2014-01-01

    Background: The aim of the study was to investigate the effects of dietary combination of Nigella sativa seed and oil extracts with chloroquine (CQ), and how these combinations enhance CQ efficacy in mice infected with Plasmodium berghei and their survival rates. Materials and Methods: Chloroquine sensitive P. berghei, NK65 strain was used for the study. This was passaged intraperitoneally into albino mice with a 0.2ml standard inoculum consisting of 106 parasitized erythrocyte suspension in phosphate buffer solution (PBS). Parasitaemia was ascertained by microscopical examination of blood films under oil immersion at X100 magnification. Results: Nigella sativa seed in feed (NSSF), NSSF + CQ on day 4, produced 86.1% and 86.0% suppression respectively, while Nigella sativa oil extract in feed (NSOF) and in combination with CQ had 86.0% and 99.9% suppression respectively. The degree of suppression with the combination was significantly higher compared to CQ alone (P < 0.001) (36.1%). Complete parasitaemia clearance was obtained on the 20th and 15th day of treatment for NSSF, NSSF + CQ respectively, while that for NSOF and NSOF + CQ was on days 26 and 12 respectively. For CQ parasite clearance was 12 days with treatment. Also, the combinastion of 10 mg/kg Nigella sativa oil treatment injected intraperitoneally with oral CQ produced very significant parasite suppression (P < 0.0001) (93%). Survival rate in NSSF and NSOF and in combination with CQ groups was 100 and 60.0% for CQ alone. Conclusions: This study shows that the use of Nigella sativa seed and oil extract as dietary supplements in combination with CQ has a potential in enhancing the efficacy of CQ and could be of benefit in management of malaria. PMID:24991115

  20. Studying the effect of chloroquine on sporozoite-induced protection and immune responses in Plasmodium berghei malaria

    NARCIS (Netherlands)

    Bijker, E.M.; Nganou Makamdop, C.K.; Gemert, G.J.A. van; Zavala, F.; Cockburn, I.; Sauerwein, R.W.

    2015-01-01

    BACKGROUND: Sporozoite immunization of animals and humans under a chemo-prophylactic cover of chloroquine (CPS-CQ) efficiently induces sterile protection against malaria. In humans, CPS-CQ is strikingly more efficient than immunization with radiation attenuated sporozoites (RAS), raising the

  1. Antimalarial activity of Malaysian Plectranthus amboinicus against Plasmodium berghei

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    Norazsida Ramli

    2014-01-01

    Full Text Available Context: Malaria is a mosquito-borne disease caused by parasitic protozoa from the genus of Plasmodium. The protozoans have developed resistance against many of current drugs. It is urgent to find an alternative source of new antimalarial agent. In the effort to discover new antimalarial agents, this research has been conducted on Plectranthus amboinicus. Aims: This study was conducted to evaluate the toxicity and antiplasmodial properties of P. amboinicus. Materials and Methods: Acute oral toxicity dose at 5000 mg/kg was conducted to evaluate the safety of this extract. Twenty mice were divided into control and experimental group. All the mice were observed for signs of toxicity, mortality, weight changes and histopathological changes. Antimalarial activity of different extract doses of 50, 200, 400 and 1000 mg/kg were tested in vivo against Plasmodium berghei infections in mice (five mice for each group during early, established and residual infections. Results: The acute oral toxicity test revealed that no mortality or evidence of adverse effects was seen in the treated mice. The extract significantly reduced the parasitemia by the 50 (P = 0.000, 200 (P = 0.000 and 400 mg/kg doses (P = 0.000 in the in vivo prophylactic assay. The percentage chemo-suppression was calculated as 83.33% for 50 mg/kg dose, 75.62% for 200 mg/kg dose and 90.74% for 400 mg/kg dose. Body weight of all treated groups; T1, T2, T3 and T4 also showed enhancement after 7 days posttreatment. Statistically no reduction of parasitemia calculated for curative and suppressive test. Conclusion: Thus, this extract may give a promising agent to be used as a prophylactic agent of P. berghei infection.

  2. STUDI IMUNOSTIMULAN EKSTRAK TOMAT PADA INFEKSI PLASMODIUM BERGHEI

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    Retno Sri Iswari

    2013-02-01

    Full Text Available Abstrak. Alternatif penanggulangan kasus malaria melalui peningkatan status imunitas tubuh sehingga tidak terjadi penyakit karena infeksi Plasmodium atau untuk mengurangi bahkan membunuh parasit tersebut adalah menggunakan tomat (Lycopersicum esculentum Mill. Penelitian dilakukan menggunakan disain penelitian Posttest Randomized Control Group Desain. Rancangan penelitian menggunakan Rancangan Acak Lengkap dengan 5 perlakuan, setiap perlakuan dengan 7 ulangan. Kelompok kontrol negatif (K diberi pakan standart, Kelompok kontrol positif (K + - , diberi pakan standart dan klorokuin dan diberi klorokuin. Kelompok perlakuan (P 1 .P 2 dan P diberi pakan standart dan ekstrak tomat dengan dosis 0,1. 1, dan 10 mg/kgBB/hari per oral selama 16 hari. Pada hari ke-17 semua kelompok diinfeksi dengan 10 7 3 Plasmodium berghei intraperitonial. Pada hari ke-8 setelah mencit diinfeksi mencit dibunuh, kemudian dilakukan pemeriksaan IFN-?, IL-4 dan IL-12. Data dianalisis dengan analisa varians (ANOVA satu jalan, dilanjutkan dengan Least Significant Difference (LSD. Hasil uji LSD pada kadar IFN-?, IL-4 dan IL-12 menunjukkan perbedaan yang bermakna (p?0,05, antara yang diberi ekstrak tomat (P 2 dan P dengan yang tidak diberi ekstrak tomat (K - dan K + 3 , kecuali untuk yang diberi ekstrak tomat 0,1 mg/KgBB tidak menunjukkan perbedaan yang bermakna dengan yang tidak diberi ekstrak tomat. Kesimpulan penelitian adalah dosis yang paling efektif meningkatkan status imunitas tubuh untuk mengurangi bahkan membunuh parasit dalam tubuh adalah pemberian ekstrak tomat dengan dosis 10 mg/kgBB/hari.

  3. Differential gene expression in abdomens of the malaria vector mosquito, Anopheles gambiae, after sugar feeding, blood feeding and Plasmodium berghei infection

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    Romans Patricia A

    2006-05-01

    Full Text Available Abstract Background Large scale sequencing of cDNA libraries can provide profiles of genes expressed in an organism under defined biological and environmental circumstances. We have analyzed sequences of 4541 Expressed Sequence Tags (ESTs from 3 different cDNA libraries created from abdomens from Plasmodium infection-susceptible adult female Anopheles gambiae. These libraries were made from sugar fed (S, rat blood fed (RB, and P. berghei-infected (IRB mosquitoes at 30 hours after the blood meal, when most parasites would be transforming ookinetes or very early oocysts. Results The S, RB and IRB libraries contained 1727, 1145 and 1669 high quality ESTs, respectively, averaging 455 nucleotides (nt in length. They assembled into 1975 consensus sequences – 567 contigs and 1408 singletons. Functional annotation was performed to annotate probable molecular functions of the gene products and the biological processes in which they function. Genes represented at high frequency in one or more of the libraries were subjected to digital Northern analysis and results on expression of 5 verified by qRT-PCR. Conclusion 13% of the 1965 ESTs showing identity to the A. gambiae genome sequence represent novel genes. These, together with untranslated regions (UTR present on many of the ESTs, will inform further genome annotation. We have identified 23 genes encoding products likely to be involved in regulating the cellular oxidative environment and 25 insect immunity genes. We also identified 25 genes as being up or down regulated following blood feeding and/or feeding with P. berghei infected blood relative to their expression levels in sugar fed females.

  4. Antimalarial effect of agmatine on Plasmodium berghei K173 strain

    Institute of Scientific and Technical Information of China (English)

    SURui-Bin; WEIXiao-Li; LIUYin; LIJin

    2003-01-01

    AIM: To study the antimalarial effect of agmatine (Agm) on chloroquine-susceptible Plasmodium berghei K173strain (S strain) and the P berghei K173 resistant strain (R strain). METHODS: The antimalarial effects of Agm onP berghei K173 S strain and R strain were evaluated by Peters 4-d suppression test in mice. RESULTS: Agm(12.5-200 mg/kg,ig,daily) decreased the parasitemia for both P berghei K173 S strain (IC50=139 mg/kg) and Rstrain (IC50=126mg/kg) in mice. Subcutaneous injection (sc) of Agm (5-40mg/kg,tid) showed relatively strongerantimalarial effect than intragastric gavage (IC50=30 mg/kg) in P berghei K 173 S strain. Spermidine antagonized theantimalarial effect of Agm for P berghei K173 S strain and R strain. Agm did not reverse the chloroquine resistanceof P berghei K173 S strain, dl-α-Difluoromethylornithine (DFMO, sc) decreased the parasitemia of P BergheiK173 S strain and this effect was antagonized by spermidine. CONCLUSION: Agm has an antimalarial effect andthe mechanism is related to its inhibition of polyamine synthesis.

  5. Nauclea latifolia aqueous leaf extract eliminates hepatic and cerebral Plasmodium berghei parasite in experimental mice

    Institute of Scientific and Technical Information of China (English)

    Innocent Onyesom; Ejovi Osioma; Precious Chiamaka Okereke

    2015-01-01

    Objective:To assess the effects of hot water leaf extract of Nauclea latifolia (N. latifolia) on antioxidant status, lipid peroxidation values and parasite levels in hepatic and brain tissue of experimental mice (BALB/c) infected with Plasmodium berghei (P. berghei) malaria. Methods:Forty nine mice were divided into seven groups (n=7) and used for the study. Group A (control) were given 0.2 mL/kg phosphate buffer saline;Group B mice were infected with P. berghei and treated with phosphate buffer saline. Groups C and D mice were also infected but treated with 200 and 300 mg/kg body weight of leaf extract respectively. Groups E and F mice were not infected, but received 200 and 300 mg/kg of leaf extract respectively. Group G mice were infected and treated with chloroquine (5 mg/kg). Liver and brain tissues of mice were prepared for both biochemical assay and microscopic examination. Results:Results showed that P. berghei malaria infection induced oxidative stress in both liver and brain tissues as evidenced by the significant (P Conclusions:The bioactive phytochemical(s) in N. latifolia should be structured and the mechanism(s) of its antimalarial tendency should be further investigated.

  6. The interplay between tubulins and P450 cytochromes during Plasmodium berghei invasion of Anopheles gambiae midgut.

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    Rute C Félix

    Full Text Available BACKGROUND: Plasmodium infection increases the oxidative stress inside the mosquito, leading to a significant alteration on transcription of Anopheles gambiae detoxification genes. Among these detoxification genes several P450 cytochromes and tubulins were differently expressed, suggesting their involvement in the mosquito's response to parasite invasion. P450 cytochromes are usually involved in the metabolism and detoxification of several compounds, but are also regulated by several pathogens, including malaria parasite. Tubulins are extremely important as components of the cytoskeleton, which rearrangement functions as a response to malaria parasite invasion. METHODOLOGY/PRINCIPAL FINDINGS: Gene silencing methods were used to uncover the effects of cytochrome P450 reductase, tubulinA and tubulinB silencing on the A. gambiae response to Plasmodium berghei invasion. The role of tubulins in counter infection processes was also investigated by inhibiting their effect. Colchicine, vinblastine and paclitaxel, three different tubulin inhibitors were injected into A. gambiae mosquitoes. Twenty-four hours post injection these mosquitoes were infected with P. berghei through a blood meal from infected CD1 mice. Cytochrome P450 gene expression was measured using RT-qPCR to detect differences in cytochrome expression between silenced, inhibited and control mosquitoes. Results showed that cytochrome P450 reductase silencing, as well as tubulin (A and B silencing and inhibition affected the efficiency of Plasmodium infection. Silencing and inhibition also affected the expression levels of cytochromes P450. CONCLUSIONS: Our results suggest the existence of a relationship between tubulins and P450 cytochromes during A. gambiae immune response to P. berghei invasion. One of the P450 cytochromes in this study, CYP6Z2, stands out as the potential link in this association. Further work is needed to fully understand the role of tubulin genes in the response to

  7. Bone marrow chimeric mice reveal a dual role for CD36 in Plasmodium berghei ANKA infection

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    Febbraio Maria

    2007-03-01

    Full Text Available Abstract Background Adhesion of Plasmodium-infected red blood cells (iRBC to different host cells, ranging from endothelial to red blood cells, is associated to malaria pathology. In vitro studies have shown the relevance of CD36 for adhesion phenotypes of Plasmodium falciparum iRBC such as sequestration, platelet mediated clumping and non-opsonic uptake of iRBC. Different adhesion phenotypes involve different host cells and are associated with different pathological outcomes of disease. Studies with different human populations with CD36 polymorphisms failed to attribute a clear role to CD36 expression in human malaria. Up to the present, no in vivo model has been available to study the relevance of different CD36 adhesion phenotypes to the pathological course of Plasmodium infection. Methods Using CD36-deficient mice and their control littermates, CD36 bone marrow chimeric mice, expressing CD36 exclusively in haematopoietic cells or in non-haematopoietic cells, were generated. Irradiated CD36-/- and wild type mice were also reconstituted with syngeneic cells to control for the effects of irradiation. The reconstituted mice were infected with Plasmodium berghei ANKA and analysed for the development of blood parasitaemia and neurological symptoms. Results All mice reconstituted with syngeneic bone marrow cells as well as chimeric mice expressing CD36 exclusively in non-haematopoietic cells died from experimental cerebral malaria between day 6 and 12 after infection. A significant proportion of chimeric mice expressing CD36 only in haematopoietic cells did not die from cerebral malaria. Conclusion The analysis of bone marrow chimeric mice reveals a dual role of CD36 in P. berghei ANKA infection. Expression of CD36 in haematopoietic cells, most likely macrophages and dendritic cells, has a beneficial effect that is masked in normal mice by adverse effects of CD36 expression in non-haematopoietic cells, most likely endothelial cells.

  8. Effect of pre-existing Schistosoma haematobium infection on Plasmodium berghei multiplications in imprinting control region mice

    Institute of Scientific and Technical Information of China (English)

    Benjamin; Amoani; Elvis; Ofori; Ameyaw; Du-Bois; Asante; Francis; Ackah; Armah; James; Prah; Collins; Paa; Kwesi; Botchey; Johnson; Nyarko; Boampong

    2015-01-01

    Objective: To investigate the effect of pre-existing Schistosoma haematobium(S. haematobium) infection on malaria disease severity.Methods: The study involved the use of twenty-i ve imprinting control region mice, i fteen of which were initially infected with S. haematobium. Five of the remaining ten schistouninfected mice together with i ve schisto-infected mice were infected with Plasmodium berghei(P. berghei) after four weeks(acute stage) of schistosoma infection. The remaining i ve schisto-uninfected mice together with i ve schisto-infected mice were also infected with P. berghei after seven weeks(chronic stage) of schistosoma infection. The last i ve schistoinfected mice were used as control group. They were then monitored for changes in P. berghei parasitaemia on Days 3, 5, 7, 9 and 11 post-infection. Records on their survivability were also taken.Results: The co-infected mice had signii cantly higher malaria parasitaemia, compared with the mono-infected mice during acute S. haematobium infection. In contrast, the co-infected mice had signii cantly lower malaria parasitaemia during chronic S. haematobium infection and a higher survival rate.Conclusions: Co-infection of mice with P. berghei during acute S. haematobium infection resulted in rapid P. berghei development and increased malaria parasitaemia. However, the co-infection resulted in slower P. berghei development and decreased malaria parasitaemia with enhanced survivability of the mice during chronic S. haematobium infection. Therefore, pre-existing chronic S. haematobium infection may provide some protection to the host by reducing parasitaemia.

  9. Inhibition of In Vivo Growth of Plasmodium berghei by Launaea taraxacifolia and Amaranthus viridis in Mice

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    Olorunnisola, Olubukola S.; Adegbola, Peter

    2016-01-01

    Launaea taraxacifolia and Amaranthus viridis used by people of Western Africa in the treatment of malaria and related symptoms were assessed for their antiplasmodial value against the chloroquine sensitive strain of Plasmodium berghei. Crude extracts (200 mg/kg) and chloroquine (5 mg/kg) were administered to different groups of Swiss mice. The percentage of parasitemia, survival time, and haematological parameters were determined. Both extracts significantly (p phytochemical investigations in the search for new and locally affordable antimalarial agents. PMID:28050307

  10. Methylene blue inhibits lumefantrine-resistant Plasmodium berghei.

    Science.gov (United States)

    Mwangi, Victor Irungu; Mumo, Ruth Mwende; Kiboi, Daniel Muthui; Omar, Sabah Ahmed; Ng'ang'a, Zipporah Waithera; Ozwara, Hastings Suba

    2016-06-30

    Chemotherapy still is the most effective way to control malaria, a major public health problem in sub-Saharan Africa. The large-scale use of the combination therapy artemether-lumefantrine for malaria treatment in Africa predisposes lumefantrine to emergence of resistance. There is need to identify drugs that can be used as substitutes to lumefantrine for use in combination therapy. Methylene blue, a synthetic anti-methemoglobinemia drug, has been shown to contain antimalarial properties, making it a candidate for drug repurposing. The present study sought to determine antiplasmodial effects of methylene blue against lumefantrine- and pyrimethamine-resistant strains of P. berghei. Activity of methylene blue was assessed using the classical four-day test on mice infected with lumefantrine-resistant and pyrimethamine-resistant P. berghei. A dose of 45 mg/kg/day was effective for testing ED90. Parasitemia and mice survival was determined. At 45 mg/kg/day, methylene blue sustained significant parasite inhibition, over 99%, for at least 6 days post-treatment against lumefantrine-resistant and pyrimethamine-resistant P. berghei (p = 0.0086 and p = 0.0191, respectively). No serious adverse effects were observed. Our results indicate that methylene blue at a concentration of 45 mg/kg/day confers over 99% inhibition against lumefantrine- and pyrimethamine-resistant P. berghei for six days. This shows the potential use methylene blue in the development of antimalarials against lumefantrine- and pyrimethamine-resistant parasites.

  11. Effects of levamisole on experimental infections by Plasmodium berghei in mice

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    Enrique Melendez C.

    1987-12-01

    Full Text Available Levamisole (phenylimidothiazol, considered a strong immunostimulant, when administered to healthy Swiss mice did not cause a significant increase in -the weight of their thymus, liver and spleen, even though the drug was used at different times before removing such organs. High doses ofdrug used in the 4-day prophylactic scheme had no antimalarial effect. However, when given to malaria infected mice 24 hours before, at the same time, and 24 hours after the inoculation of a chloroquine-sensitive or a chloroquine-resistant strain of Plasmodium berghei small doses of the drug induced a somewhat decreased parasitemia, the dose of 1 mg/kg body weight before the inoculum being the best scheme. The mortality rates by malaria in the levamisole treated groups were also delayed although all mice finally died. The data suggest that levamisole may display a stimulant effect on the depressed immune response caused by malaria.

  12. Indigofera pulchra leaves extracts contain anti-Plasmodium berghei agents

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    Sani Ibrahim

    2011-06-01

    Full Text Available This study was conducted to investigate the anti-Plasmodium berghei activities of some extracts from Indigofera pulchra leaves. Six groups of mice were intraperitoneally infected with chloroquine sensitive P. berghei (NK 65 among which two groups were orally treated with 100 and 200 mg/kg body weight of methanol leaves extract while another two groups were treated with 100 and 200 mg/kg of n-butanol fraction derived from the methanol extract. Another infected group was treated with chloroquine (25 mg/kg whereas the remaining infected group was left untreated. All infected treated groups possessed a significantly (p<0.05 lowered number of parasitized erythrocytes than the infected untreated group throughout the experimental period except at day 6 post-infection. However, the 200 mg/kg n-butanol fraction treated group demonstrated a persistently lower number of parasitized erythrocytes than other extract-treated groups after day 9 post infection to the termination of the experiment. The P. berghei was found to induce anemia whose severity was significantly (p<0.05 ameliorated by all the treatments. It was concluded that the methanol extract and n-butanol fraction of I. pulchra contains anti-P. berghei phytochemicals that could ameliorate the parasite-induced anemia.

  13. Nauclea latifolia aqueous leaf extract eliminates hepatic and cerebral Plasmodium berghei parasite in experimental mice

    Institute of Scientific and Technical Information of China (English)

    Innocent; Onyesom; Ejovi; Osioma; Precious; Chiamaka; Okereke

    2015-01-01

    Objective: To assess the effects of hot water leaf extract of Nauclea latifolia(N. latifolia) on antioxidant status, lipid peroxidation values and parasite levels in hepatic and brain tissue of experimental mice(BALB/c) infected with Plasmodium berghei(P. berghei) malaria.Methods: Forty nine mice were divided into seven groups(n = 7) and used for the study. Group A(control) were given 0.2 m L/kg phosphate buffer saline; Group B mice were infected with P. berghei and treated with phosphate buffer saline. Groups C and D mice were also infected but treated with 200 and 300 mg/kg body weight of leaf extract respectively. Groups E and F mice were not infected, but received 200 and 300 mg/kg of leaf extract respectively. Group G mice were infected and treated with chloroquine(5 mg/kg). Liver and brain tissues of mice were prepared for both biochemical assay and microscopic examination. Results: Results showed that P. berghei malaria infection induced oxidative stress in both liver and brain tissues as evidenced by the significant(P < 0.05) decrease in antioxidants: superoxide dismutase, reduced glutathione and catalase. These reductions perhaps caused compromise in membrane integrity as indicated by the significant increase in lipid peroxidation product malondialdhyde. Malaria parasites were also identified in these tissues. However, N. latifolia treatment eliminated the parasites in tissues and protected them from oxidative damage even better than chloroquine treatment did, whose anti-malarial potency also cleared tissue parasites. The measurement of protection by N. latifolia against damage was strengthened by the insignificant micro structural alterations.Conclusions: The bioactive phytochemical(s) in N. latifolia should be structured and the mechanism(s) of its antimalarial tendency should be further investigated.

  14. Antihemolytic Activities of Green Tea, Safflower, and Mulberry Extracts during Plasmodium berghei Infection in Mice

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    Suthin Audomkasok

    2014-01-01

    Full Text Available Malaria-associated hemolysis is associated with mortality in adult patients. It has been speculated that oxidative stress and inflammation induced by malaria parasite are involved in its pathophysiology. Hence, we aimed to investigate the antihemolytic effect of green tea, safflower, and mulberry extracts against Plasmodium berghei infection. Aqueous crude extracts of these plants were prepared using hot water method and used for oral treatment in mice. Groups of ICR mice were infected with 6 × 106 infected red blood cells of P. berghei ANKA by intraperitoneal injection and given the extracts (500, 1500, and 3000 mg/kg twice a day for 4 consecutive days. To assess hemolysis, hematocrit levels were then evaluated. Malaria infection resulted in hemolysis. However, antihemolytic effects were observed in infected mice treated with these extracts at dose-dependent manners. In conclusion, aqueous crude extracts of green tea, safflower, and mulberry exerted antihemolysis induced by malaria infection. These plants may work as potential source in the development of variety of herbal formulations for malarial treatment.

  15. The Maternally Inheritable Wolbachia wAlbB Induces Refractoriness to Plasmodium berghei in Anopheles stephensi

    Science.gov (United States)

    Joshi, Deepak; Pan, Xiaoling; McFadden, Michael J.; Bevins, David; Liang, Xiao; Lu, Peng; Thiem, Suzanne; Xi, Zhiyong

    2017-01-01

    The endosymbiont Wolbachia wAlbB induces refractoriness to Plasmodium falciparum in Anopheles stephensi, the primary mosquito vector of human malaria in the Middle East and South Asia. However, it remains unknown whether such refractoriness can be extended to other malaria species. In particular, it was reported that under very specific conditions, wAlbB can enhance Plasmodium infection in some hosts. Here, we measured the impact of wAlbB on the rodent malaria parasite Plasmodium berghei in A. stephensi by comparing the load of oocysts and sporozoites in midguts and salivary glands, respectively, between wAlbB-infected and -uninfected mosquitoes. To investigate whether wAlbB modulated mosquito immune defense against parasites, we compared the expression of the immune genes, which were previously reported to involve in antimalarial response, in both midguts and the remaining carcass tissues of mosquitoes. The stable association of wAlbB with A. stephensi resulted in reduction of parasites by more than half at the oocyst stage, and up to 91.8% at the sporzoite stage. The anti-plasmodium immune genes, including TEP1, LRIM1, Toll pathway gene Rel1 and the effector Defensin 1, were induced by wAlbB in different mosquito body tissues. These findings suggest that immune priming is a potential cause of wAlbB-mediated antimalarial response in A. stephensi. More importantly, no evidence was found for any enhancement of Plasmodium infection in A. stephensi stably infected with wAlbB. We discuss these findings with possible implementations of Wolbachia for malaria control in disease endemic areas. PMID:28337184

  16. Excess Fibrin Deposits Decrease Fetal Weight of Pregnant Mice Infected by Plasmodium berghei

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    Desy Andari

    2014-05-01

    Full Text Available Low birth weight is commonly attributed to malaria in pregnancy, but the cellular and molecular mechanisms that underlie this poor birth outcome are incompletely understood. A universally described histopathological feature of placental malaria is excessive deposition of fibrin, the end-product of the coagulation cascade. This study was conducted to compare fibrin deposit in pregnant mice that infected by Plasmodium berghei (treatment group to the normal pregnant mice (control group and its association with fetal weight. This research is in vivo experimental laboratory study that used 18 pregnant Balb/c mice which divided to the control the group (8 mice and treatment group (9 mice infected by P.berghei. Placentas were staining with Haematoxylin-Eosin (HE for fibrin deposits examination whereas fetal weight was performed with Mettler analytical balance AE 50. Fetal weight of the treatment group was lower than those of the control group (t test, p=0,002. Fibrin deposits were increased in the treatment group (t test, p=0,005 and influenced weight of fetuses (Spearman r= -0,586, p= 0,014. Weights of fetuses are interfered by fibrin deposits during malaria infection.

  17. Studies on the effects of sida acuta and vetiveria zizanioides against the malarial vector, anopheles stephensi and malarial parasite, plasmodium berghei

    Science.gov (United States)

    Methanolic extracts of Sida acuta and Vetiveria zizanioides leaves and root were studied for toxicity to Anopheles stephensi mosquitoes and to the malaria parasite Plasmodium berghei in mice. The extracts reduced parasitemia levels in mice by 17-69%, depending on extract concentration. Median le...

  18. Influence of CD4+CD25+ T cells on Plasmodium berghei NK65 infection in BALB/c mice.

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    Long, Ton That Ai; Nakazawa, Shusuke; Onizuka, Shozaburo; Huaman, Maria Cecilia; Kanbara, Hiroji

    2003-02-01

    CD4(+) T cells co-expressing CD25 (CD4(+)CD25(+) T cells) have been identified as immunoregulatory suppressors modulating autoimmune response. Beside that, autoimmune response was supposed to be associated with malaria infection. Based on these data, we hypothesised that CD4(+)CD25(+) T cells may influence protective immunity to malaria parasites, while suppressing autoimmune response arising throughout the course of malarial infection. To test this possibility, we evaluated the kinetics of CD4(+)CD25(+) T cells during malaria infection and investigated the influence of CD25 depletion by anti-mouse CD25 monoclonal antibody (PC61) on the infection, using a mouse model of premunition to Plasmodium berghei NK65 malaria. The results showed that, during exacerbation of P. berghei NK65 infection, the proportion of CD4(+)CD25(+) T cells among CD4(+) T cells decreased, although that of CD4(+) T cells increased. CD25 depletion clearly delayed the growth of parasitaemia during parasite challenge, particularly in immunised mice. These findings demonstrated that CD4(+)CD25(+) T cells are able to influence protective immunity underlying premunition to P. berghei NK65 parasites.

  19. Germinal center architecture disturbance during Plasmodium berghei ANKA infection in CBA mice

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    Pelajo-Machado Marcelo

    2007-05-01

    Full Text Available Abstract Background Immune responses to malaria blood stage infection are in general defective, with the need for long-term exposure to the parasite to achieve immunity, and with the development of immunopathology states such as cerebral malaria in many cases. One of the potential reasons for the difficulty in developing protective immunity is the poor development of memory responses. In this paper, the potential association of cellular reactivity in lymphoid organs (spleen, lymph nodes and Peyer's patches with immunity and pathology was evaluated during Plasmodium berghei ANKA infection in CBA mice. Methods CBA mice were infected with 1 × 106 P. berghei ANKA-parasitized erythrocytes and killed on days 3, 6–8 and 10 of infection. The spleen, lymph nodes and Peyer's patches were collected, fixed in Carson's formalin, cut in 5 μm sections, mounted in glass slides, stained with Lennert's Giemsa and haematoxylin-eosin and analysed with bright-field microscopy. Results Early (day 3 strong activation of T cells in secondary lymphoid organs was observed and, on days 6–8 of infection, there was overwhelming activation of B cells, with loss of conventional germinal center architecture, intense centroblast activation, proliferation and apoptosis but little differentiation to centrocytes. In the spleen, the marginal zone disappeared and the limits between the disorganized germinal center and the red pulp were blurred. Intense plasmacytogenesis was observed in the T cell zone. Conclusion The observed alterations, especially the germinal center architecture disturbance (GCAD with poor centrocyte differentiation, suggest that B cell responses during P. berghei ANKA infection in mice are defective, with potential impact on B cell memory responses.

  20. Proteomic and genetic analyses demonstrate that Plasmodium berghei blood stages export a large and diverse repertoire of proteins.

    Science.gov (United States)

    Pasini, Erica M; Braks, Joanna A; Fonager, Jannik; Klop, Onny; Aime, Elena; Spaccapelo, Roberta; Otto, Thomas D; Berriman, Matt; Hiss, Jan A; Thomas, Alan W; Mann, Matthias; Janse, Chris J; Kocken, Clemens H M; Franke-Fayard, Blandine

    2013-02-01

    Malaria parasites actively remodel the infected red blood cell (irbc) by exporting proteins into the host cell cytoplasm. The human parasite Plasmodium falciparum exports particularly large numbers of proteins, including proteins that establish a vesicular network allowing the trafficking of proteins onto the surface of irbcs that are responsible for tissue sequestration. Like P. falciparum, the rodent parasite P. berghei ANKA sequesters via irbc interactions with the host receptor CD36. We have applied proteomic, genomic, and reverse-genetic approaches to identify P. berghei proteins potentially involved in the transport of proteins to the irbc surface. A comparative proteomics analysis of P. berghei non-sequestering and sequestering parasites was used to determine changes in the irbc membrane associated with sequestration. Subsequent tagging experiments identified 13 proteins (Plasmodium export element (PEXEL)-positive as well as PEXEL-negative) that are exported into the irbc cytoplasm and have distinct localization patterns: a dispersed and/or patchy distribution, a punctate vesicle-like pattern in the cytoplasm, or a distinct location at the irbc membrane. Members of the PEXEL-negative BIR and PEXEL-positive Pb-fam-3 show a dispersed localization in the irbc cytoplasm, but not at the irbc surface. Two of the identified exported proteins are transported to the irbc membrane and were named erythrocyte membrane associated proteins. EMAP1 is a member of the PEXEL-negative Pb-fam-1 family, and EMAP2 is a PEXEL-positive protein encoded by a single copy gene; neither protein plays a direct role in sequestration. Our observations clearly indicate that P. berghei traffics a diverse range of proteins to different cellular locations via mechanisms that are analogous to those employed by P. falciparum. This information can be exploited to generate transgenic humanized rodent P. berghei parasites expressing chimeric P. berghei/P. falciparum proteins on the surface of

  1. Antimalarial activity of Malaysian Plectranthus amboinicus against Plasmodium berghei

    OpenAIRE

    Norazsida Ramli; Pakeer Oothuman Syed Ahamed; Hassan Mohamed Elhady; Muhammad Taher

    2014-01-01

    Context: Malaria is a mosquito-borne disease caused by parasitic protozoa from the genus of Plasmodium. The protozoans have developed resistance against many of current drugs. It is urgent to find an alternative source of new antimalarial agent. In the effort to discover new antimalarial agents, this research has been conducted on Plectranthus amboinicus. Aims: This study was conducted to evaluate the toxicity and antiplasmodial properties of P. amboinicus. Materials and Methods: Acute oral t...

  2. TRPV1 Antagonism by Capsazepine Modulates Innate Immune Response in Mice Infected with Plasmodium berghei ANKA

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    Elizabeth S. Fernandes

    2014-01-01

    Full Text Available Thousands of people suffer from severe malaria every year. The innate immune response plays a determinant role in host’s defence to malaria. Transient receptor potential vanilloid 1 (TRPV1 modulates macrophage-mediated responses in sepsis, but its role in other pathogenic diseases has never been addressed. We investigated the effects of capsazepine, a TRPV1 antagonist, in malaria. C57BL/6 mice received 105 red blood cells infected with Plasmodium berghei ANKA intraperitoneally. Noninfected mice were used as controls. Capsazepine or vehicle was given intraperitoneally for 6 days. Mice were culled on day 7 after infection and blood and spleen cell phenotype and activation were evaluated. Capsazepine decreased circulating but not spleen F4/80+Ly6G+ cell numbers as well as activation of both F4/80+and F4/80+Ly6G+ cells in infected animals. In addition, capsazepine increased circulating but not spleen GR1+ and natural killer (NK population, without interfering with natural killer T (NKT cell numbers and blood NK and NKT activation. However, capsazepine diminished CD69 expression in spleen NKT but not NK cells. Infection increased lipid peroxidation and the release of TNFα and IFNγ, although capsazepine-treated group exhibited lower levels of lipid peroxidation and TNFα. Capsazepine treatment did not affect parasitaemia. Overall, TRPV1 antagonism modulates the innate immune response to malaria.

  3. Study on application of high doses plasmodium berghei in cell culture

    Science.gov (United States)

    Spencer, L. M.; De Santis, M.; Davila, J.; Foinquinos, A.; Salcedo, E.; Sajo-Bohus, L.

    2012-02-01

    Malaria, one of the most important infection disease problems in the world, is caused by protozoan parasites of the genus Plasmodium. This disease is responsible for hundreds of the millions of clinical cases and more than one million deaths per year, for this reason, malaria is a priority and the WHO estimates that half of the world population is at risk. In this work we study how the absorbed dose inactivates the parasite (Plasmodium berghei) in rodent model (BALB/c mice), by applying X-ray irradiation. The dose was increased from 10 to 50 Gy in parasitized red blood cells (PRBC) with merozoite stage using in vitro short cultures. Also the reduction of the irradiation effect was determined by intra-peritoneal inoculations of irradiated parasites. Afterwards, the parasitaemia was assessed daily on smears made from tail blood and stained with Giemsa's reagent. Besides, the effect of irradiation was evaluated using an immunological test as indirect immunofluorescence assay (IFA). The results of this study showed that the most effective radiation for inactivation of parasites is about 50 Gy and the immunofluorescence pattern showed a different distribution of the fluorescence on parasites. These results showed direct correlation between the effect of irradiated parasites and parasitaemia in the group of mice infected with RBC after 50 Gy irradiation. Our results indicated that the threshold is between 30 to 50 Gy to inactivate the parasites.

  4. CSP--a model for in vivo presentation of Plasmodium berghei sporozoite antigens by hepatocytes.

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    Saidou Balam

    Full Text Available One target of protective immunity against the Plasmodium liver stage in BALB/c mice is represented by the circumsporozoite protein (CSP, and mainly involves its recognition by IFN-γ producing specific CD8+T-cells. In a previous in vitro study we showed that primary hepatocytes from BALB/c mice process Plasmodium berghei (Pb CSP (PbCSP and present CSP-derived peptides to specific H-2k(d restricted CD8+T-cells with subsequent killing of the presenting cells. We now extend these observations to an in vivo infection model in which infected hepatocytes and antigen specific T-cell clones are transferred into recipient mice inducing protection from sporozoite (SPZ challenge. In addition, using a similar protocol, we suggest the capacity of hepatocytes in priming of naïve T-cells to provide protection, as further confirmed by induction of protection after depletion of cross-presenting dendritic cells (DCs by cytochrome c (cyt c treatment or using traversal deficient parasites. Our results clearly show that hepatocytes present Plasmodium CSP to specific-primed CD8+T-cells, and could also prime naïve T-cells, leading to protection from infection. These results could contribute to a better understanding of liver stage immune response and design of malaria vaccines.

  5. In Vivo Antimalarial Activity of Annona muricata Leaf Extract in Mice Infected with Plasmodium berghei.

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    Somsak, Voravuth; Polwiang, Natsuda; Chachiyo, Sukanya

    2016-01-01

    Malaria is one of the most important infectious diseases in the world. The choice for the treatment is highly limited due to drug resistance. Hence, finding the new compounds to treat malaria is urgently needed. The present study was attempted to evaluate the antimalarial activity of the Annona muricata aqueous leaf extract in Plasmodium berghei infected mice. Aqueous leaf extract of A. muricata was prepared and tested for acute toxicity in mice. For efficacy test in vivo, standard 4-day suppressive test was carried out. ICR mice were inoculated with 10(7) parasitized erythrocytes of P. berghei ANKA by intraperitoneal injection. The extracts (100, 500, and 1000 mg/kg) were then given orally by gavage once a day for 4 consecutive days. Parasitemia, percentage of inhibition, and packed cell volume were subsequently calculated. Chloroquine (10 mg/kg) was given to infected mice as positive control while untreated control was given only distilled water. It was found that A. muricata aqueous leaf extract at doses of 100, 500, and 1000 mg/kg resulted in dose dependent parasitemia inhibition of 38.03%, 75.25%, and 85.61%, respectively. Survival time was prolonged in infected mice treated with the extract. Moreover, no mortality to mice was observed with this extract up to a dose of 4000 mg/kg. In conclusion, the A. muricata aqueous leaf extract exerted significant antimalarial activity with no toxicity and prolonged survival time. Therefore, this extract might contain potential lead molecule for the development of a new drug for malaria treatment.

  6. Enhanced depletion of glutathione and increased liver oxidative damage in aflatoxin-fed mice infected with Plasmodium berghei

    DEFF Research Database (Denmark)

    Ankrah, N A; Sittie, A; Addo, P G

    1995-01-01

    The effect of dietary aflatoxins B1 and G1 and Plasmodium berghei infection on glutathione (GSH) levels and liver status in mice was investigated. Three days after intraperitoneal injection of 0.1 x 10(6) parasitized red blood cells into the mice, there was a significant fall in blood glutathione...... levels accompanied by a significant increase in serum cholinesterase and liver malonic dialdehyde levels in the mice fed aflatoxin compared with those in the control group. The results suggested that malaria parasites can enhance depletion of host glutathione and oxidative damage of the liver in mice fed...... low levels of aflatoxins....

  7. Sex hormones modulate the immune response to Plasmodium berghei ANKA in CBA/Ca mice.

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    Legorreta-Herrera, Martha; Mosqueda-Romo, Néstor Aarón; Nava-Castro, Karen Elizabeth; Morales-Rodríguez, Ana Laura; Buendía-González, Fidel Orlando; Morales-Montor, Jorge

    2015-07-01

    Susceptibility to malaria differs between females and males, and this sexual dimorphism may have important implications for the effects of vaccines and drugs. However, little is known about the mechanisms mediating these sexual differences. Because the main differences between sexes are dictated by sex hormones, we studied the effect of gonadal steroids on immune responses to malaria in CBA/Ca mice. We decreased sex hormones levels by gonadectomy and evaluated the splenic index and the cells involved in the immune response, including T cells (CD3(+), CD4(+), CD8(+) and NK(+)), B cells and macrophages (Mac-3(+)) in the spleens of female and male mice infected with Plasmodium berghei ANKA. In addition, we measured antibody and cytokine levels in blood. Gonadectomy increased T(+) and B(+) splenic cells in both sexes but increased Mac-3(+) cells only in male mice. By contrast, gonadectomy decreased the NK(+) cell population only in male mice. In general, female mice developed higher antibody levels than males. Contrary to our expectations, gonadectomy increased the synthesis of IgG1, IgG2b, IgG3, and total IgG in female mice, indicating negative regulation of antibody production by female sex hormones. Gonadectomy increased the synthesis of tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) only in female mice, suggesting that female sex hormones have anti-inflammatory properties. This work demonstrates that the levels of sex hormones affect the immune response and should be considered when designing malaria vaccines.

  8. Roles of the amino terminal region and repeat region of the Plasmodium berghei circumsporozoite protein in parasite infectivity.

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    Cassandra Aldrich

    Full Text Available The circumsporozoite protein (CSP plays a key role in malaria sporozoite infection of both mosquito salivary glands and the vertebrate host. The conserved Regions I and II have been well studied but little is known about the immunogenic central repeat region and the N-terminal region of the protein. Rodent malaria Plasmodium berghei parasites, in which the endogenous CS gene has been replaced with the avian Plasmodium gallinaceum CS (PgCS sequence, develop normally in the A. stephensi mosquito midgut but the sporozoites are not infectious. We therefore generated P. berghei transgenic parasites carrying the PgCS gene, in which the repeat region was replaced with the homologous region of P. berghei CS (PbCS. A further line, in which both the N-terminal region and repeat region were replaced with the homologous regions of PbCS, was also generated. Introduction of the PbCS repeat region alone, into the PgCS gene, did not rescue sporozoite species-specific infectivity. However, the introduction of both the PbCS repeat region and the N-terminal region into the PgCS gene completely rescued infectivity, in both the mosquito vector and the mammalian host. Immunofluorescence experiments and western blot analysis revealed correct localization and proteolytic processing of CSP in the chimeric parasites. The results demonstrate, in vivo, that the repeat region of P. berghei CSP, alone, is unable to mediate sporozoite infectivity in either the mosquito or the mammalian host, but suggest an important role for the N-terminal region in sporozoite host cell invasion.

  9. Protection of renal function by four selected plant extracts during Plasmodium berghei infection

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    Adewale Adetutu

    2015-10-01

    Full Text Available Background: Weakening of renal function from reactive oxygen species generated during malaria infection is one of the prominent causes of death in prevalent regions. The potential toxicity of free radical generated by malaria parasites are counteracted by a large number of cytoprotective phytochemicals. Therefore, this study examined the influence of extracts of five selected antimalarial plants (Azadirachta indica, Parquetina nigrescens, Citrus paradisi, and Khaya senigalensis on reduction of inflammation in renal tissue, blood urea nitrogen and creatinine levels during malaria infection using Plasmodium berghei infected Swiss albino mice. For in vivo assay, mice were inoculated with 1 × 107 parasitized erythrocytes and plant extracts were subsequently administered orally at 100 mg/kg body weight once a day for 17 consecutive days. The chemo-suppressive and prophylaxis effects of the plant extracts against P. berghei were investigated and compared with those of standard antimalarial drug, chloroquine. Tail bleeding was performed to check the percentage parasitaemia by making a thin film smear on a slide, stained in Giemsa. The numbers of parasited cells against the unparasitised cells were counted using a microscope. The effect of malaria infection on renal tissue was assessed by histological analysis and measurement of blood urea nitrogen and creatinine levels in plasma. At 100 mg/kg per body weight, aqueous extract of K. senegalensis, A. indica, C. paradisi and P. nigrescens exhibited significant (p<0.05 percentage inhibition and chemo-suppressive effects in comparison with the chloroquine treated mice. The result of the untreated group showed that there was a significant (p<0.05 increase in the level of plasma urea while the level of the groups treated with plants extract stabilized the level of urea and creatinine in the blood. Also there was a pathological lesion on the kidney tissue of untreated group whereas the group treated with

  10. Effects of levamisole on experimental infections by Plasmodium berghei in mice

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    Enrique Melendez C.

    1987-12-01

    Full Text Available Levamisole (phenylimidothiazol, considered a strong immunostimulant, when administered to healthy Swiss mice did not cause a significant increase in -the weight of their thymus, liver and spleen, even though the drug was used at different times before removing such organs. High doses ofdrug used in the 4-day prophylactic scheme had no antimalarial effect. However, when given to malaria infected mice 24 hours before, at the same time, and 24 hours after the inoculation of a chloroquine-sensitive or a chloroquine-resistant strain of Plasmodium berghei small doses of the drug induced a somewhat decreased parasitemia, the dose of 1 mg/kg body weight before the inoculum being the best scheme. The mortality rates by malaria in the levamisole treated groups were also delayed although all mice finally died. The data suggest that levamisole may display a stimulant effect on the depressed immune response caused by malaria.Levamisol (fenilimidotiazol, considerado urn potente imunoestimulante, quando administrado a camundongos suíços não causou aumento significante nos pesos do timo, figado ou baço, apesar de a droga ter sido usada em diferentes tempos antes da remoção desses órgãos. Doses elevadas da droga usadas no esquema profilático de 4 dias não tiveram efeito antimalárico. Entretanto quando dada a camundongos com malária, 24 horas antes, ao mesmo tempo ou 24 horas após inoculação de uma cepa de Plasmodium berghei cloroquina-sensível ou uma cepa cloroquina- resistente o levamisol reduziu, ainda que discretamente, a parasitemia nos grupos tratados, sendo a dose de 1 mg/kg o melhor esquema. Foi observado também atraso na mortalidade por malária nos grupos tratados com o levamisol. No entanto, todos os animais morreram. Os dados sugerem que o levamisol tem efeito imunoestimulante, ainda que discreto, na resposta imune de animais, deprimida pela malária.

  11. Antimalarial Potential of Carica papaya and Vernonia amygdalina in Mice Infected with Plasmodium berghei

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    Oche Okpe

    2016-01-01

    Full Text Available The study determined if administration of Vernonia amygdalina and Carica papaya plants provides synergistic effects in ameliorating plasmodium infection in mice. Thirty mice (17.88–25.3 g were divided into 6 groups of 5 mice each. Group 1 was normal control, while groups 2–6 were intraperitoneally inoculated 2.5 × 107 Plasmodium berghei parasitized red blood cell, followed by daily administration of 350 mg/kg aqueous leaf extracts after establishment of infection. Group 2 was disease control, while group 6 was treated with standard drug for four consecutive days. The results showed significant (P0.05 change in mean body weight of all treated groups except in disease control group. Histological studies of the infected mice indicate recovery of hepatic cells from congested black pigmentation. The reduction in parasite load and recovery of hepatic cell damage/hematological parameters were induced by these plant extracts. This highlighted the important usage of the plant in traditional remedy of malaria infection.

  12. Efeito de Momordica charantia I. Em camundongos infectados por Plasmodium berghei

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    Helene Mariko Ueno

    1996-10-01

    Full Text Available A Organização Mundial de Saúde (OMS citou a malãria como um dos principais problemas de saúde no Brasil e no terceiro mundo, onde 80% da população recorre à medicina tradicional (popular para sanar vários problemas de assistência médica primária. No que se refere à malária, seu tratamento e controle têm sido dificultados devido às cepas resistentes às drogas comumente utilizadas. Isso torna urgente a busca de novas drogas antimaláncas. Sabe-se que a população utiliza-se de diferentes plantas para o tratamento e cura de vários males, inclusive a malãria. Neste trabalho nos propusemos reavaliar o efeito de Momordica charantia L. (Cucurbitaceae sobre camundongos infectados por Plasmodium berghei. A planta foi testada sob a forma de extratos aquoso e etanólico, na dose de lOOOmg por kg cle peso coipóreo do camundongo, ministrado por via oral, por cinco dias consecutivos da infecção (2º ao 6º. O efeito foi avaliado em função da parasitemia e da sobrevida dos animais. Embora a população indique e utilize essa planta na malária humana, nos ensaios deste trabalho, nas condições do experimento, os extratos de M. charantia não apresentaram atividade satisfatória contra o P. berghei.According to the World Health Organization malaria is one of the major public health problems in Brazil and all over developing countries, where 80% of the population use traditional medicine to solve their primary medical problems. Both treatment and control of this parasitosis have become difficult, because of parasite strains that are resistant to conventional drugs, such as chloroquine. That makes the search for new antimalarial drugs not only important but urgent. We aimed therefore at evaluating the effects of Momordica charantia L. (Cucurbitaceae in mice infected with Plasmodium berghei. We used aquose and ethanotic extracts in a dose of 1OOOmg/kg of body weight, orally, for five consecutive days (i.e. from day 2 to day 6

  13. Protective immune mechanisms against pre-erythrocytic forms of Plasmodium berghei depend on the target antigen

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    Elke S. Bergmann-Leitner

    2014-01-01

    Full Text Available Pre-erythrocytic malaria vaccines are believed to either stop the injected sporozoites from reaching the liver or to direct cellular immune responses towards eliminating infected hepatocytes. The present study reveals for the first time the anatomical sites at which these immune mechanisms act against the malaria parasites. To determine the mechanisms leading to protection mediated by two previously characterized vaccines against either the circumsporozoite protein (CSP or the cell traversal protein for ookinetes and sporozoites (CelTOS, mice were immunized and subsequently challenged by subcutaneous injection of salivary gland sporozoites of luciferase-transgenic Plasmodium berghei parasites. The In Vivo Imaging System (IVIS was used to identify the anatomical site where the vaccine-induced immune response eliminates sporozoites after injection. The data demonstrate that CSP-based immunity acts at the site of infection (skin whereas CelTOS-based immunity is only partially efficient in the skin and allows reduced levels of liver infection that can be subsequently cleared. The results of this study challenge assumptions regarding CSP-mediated immune mechanisms and call into question the validity of some commonly used assays to evaluate anti-CSP immune responses. The knowledge of the mechanism and events leading to infection or immune defense will guide supportive treatment with drugs or combination therapies and thus accelerate the development of effective antimalarial strategies.

  14. Mitochondrial peroxidase TPx-2 is not essential in the blood and insect stages of Plasmodium berghei

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    Masuda-Suganuma Hirono

    2012-11-01

    Full Text Available Abstract Background Malaria parasites actively proliferate in the body of their vertebrate and insect hosts, and are subjected to the toxic effects of reactive oxygen species. The antioxidant defenses of malaria parasites are considered to play essential roles in their survival and are thus considered promising targets for intervention. We sought to identify the cellular function of thioredoxin peroxidase-2 (TPx-2, which is expressed in the mitochondria, by disrupting the TPx-2 gene (pbtpx-2 of the rodent malaria parasite Plasmodium berghei. Findings In three independent experiments, two disruptant populations (TPx-2 KO and three wild-type parasite populations with pyrimethamine resistance (dhfr-ts/mt at the DHFR-TS locus and intact pbtpx-2 (TPx-2 WT were obtained and cloned. Null expression of TPx-2 in the KO population was confirmed by RT-PCR and Western blot analyses. The TPx-2 KO parasite developed normally in mouse erythrocytes and multiplied at a rate similar to that of the TPx-2 WT parasite during the experimental period. The peak period of gametocytemia was delayed by 1 day in the TPx-2 KO compared with that of the TPx-2 WT and the parent parasite, however, the highest gametocyte number was comparable. The number of midgut oocysts in the TPx-2 KO at 14 days post feeding was comparable to that of the TPx-2 WT. Conclusions The present finding suggests that mitochondrial Prx TPx-2 is not essential for asexual and the insect stage development of the malaria parasite.

  15. Naturally occurring triggers that induce apoptosis-like programmed cell death in Plasmodium berghei ookinetes.

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    Medhat Ali

    Full Text Available Several protozoan parasites have been shown to undergo a form of programmed cell death that exhibits morphological features associated with metazoan apoptosis. These include the rodent malaria parasite, Plasmodium berghei. Malaria zygotes develop in the mosquito midgut lumen, forming motile ookinetes. Up to 50% of these exhibit phenotypic markers of apoptosis; as do those grown in culture. We hypothesised that naturally occurring signals induce many ookinetes to undergo apoptosis before midgut traversal. To determine whether nitric oxide and reactive oxygen species act as such triggers, ookinetes were cultured with donors of these molecules. Exposure to the nitric oxide donor SNP induced a significant increase in ookinetes with condensed nuclear chromatin, activated caspase-like molecules and translocation of phosphatidylserine that was dose and time related. Results from an assay that detects the potential-dependent accumulation of aggregates of JC-1 in mitochondria suggested that nitric oxide does not operate via loss of mitochondrial membrane potential. L-DOPA (reactive oxygen species donor also caused apoptosis in a dose and time dependent manner. Removal of white blood cells significantly decreased ookinetes exhibiting a marker of apoptosis in vitro. Inhibition of the activity of nitric oxide synthase in the mosquito midgut epithelium using L-NAME significantly decreased the proportion of apoptotic ookinetes and increased the number of oocysts that developed. Introduction of a nitric oxide donor into the blood meal had no effect on mosquito longevity but did reduce prevalence and intensity of infection. Thus, nitric oxide and reactive oxygen species are triggers of apoptosis in Plasmodium ookinetes. They occur naturally in the mosquito midgut lumen, sourced from infected blood and mosquito tissue. Up regulation of mosquito nitric oxide synthase activity has potential as a transmission blocking strategy.

  16. Contribution of the Ly49E natural killer receptor in the immune response to Plasmodium berghei infection and control of hepatic parasite development.

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    Jessica Filtjens

    Full Text Available Natural killer (NK cells have different roles in the host response against Plasmodium-induced malaria depending on the stage of infection. Liver NK cells have a protective role during the initial hepatic stage of infection by production of the TH1-type cytokines IFN-γ and TNF-α. In the subsequent erythrocytic stage of infection, NK cells also induce protection through Th1-type cytokines but, in addition, may also promote development of cerebral malaria via CXCR3-induction on CD8(+ T cells resulting in migration of these cells to the brain. We have recently shown that the regulatory Ly49E NK receptor is expressed on liver NK cells in particular. The main objective of this study was therefore to examine the role of Ly49E expression in the immune response upon Plasmodium berghei ANKA infection, for which we compared wild type (WT to Ly49E knockout (KO mice. We show that the parasitemia was higher at the early stage, i.e. at days 6-7 of Plasmodium berghei ANKA infection in Ly49E KO mice, which correlated with lower induction of CD69, IFN-γ and TNF-α in DX5(- liver NK cells at day 5 post-infection. At later stages, these differences faded. There was also no difference in the kinetics and the percentage of cerebral malaria development and in lymphocyte CXCR3 expression in WT versus Ly49E KO mice. Collectively, we show that the immune response against Plasmodium berghei ANKA infection is not drastically affected in Ly49E KO mice. Although NK cells play a crucial role in Plasmodium infection and Ly49E is highly expressed on liver NK cells, the Ly49E NK receptor only has a temporarily role in the immune control of this parasite.

  17. Isolation of Plasmodium berghei ookinetes in culture using Nycodenz density gradient columns and magnetic isolation

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    Williams Jackie

    2003-11-01

    Full Text Available Abstract Background Large scale in vitro production of the mosquito stages of malaria parasites remains elusive, with only limited success for complete sporogonic development and only one report of development through to infective sporozoites. The initial step in this process is the production, in vitro, of ookinetes from gametocytaemic blood. Methods for isolation of these ookinetes from blood cells have been described; however, in addition to yield often being low, processing time and potential for contamination by erythrocytes remain high. Methods This study compares two procedures for retaining mature ookinetes from blood stage cultures, whilst removing red blood cells and other contaminants prior to further culture of the parasite. The well established method of isolation on Nycodenz cushions is compared with a novel method utilizing the innate magnetic properties of the haem pigment crystals found in the cytoplasm of ookinetes. Results Yield and viability of ookinetes were similar with both isolation methods. However, in our hands magnetic isolation produced a cleaner ookinete preparation much more quickly. Moreover, decreasing the flow rate through the magnetic column could further enhance the yield. Conclusion We recommend the enrichment of an ookinete preparation prior to further culture being performed using the magnetic properties of Plasmodium berghei ookinetes as an alternative to their density. The former technique is faster, removes more erythrocytes, but day-to-day costs are greater.

  18. Plasmodium vivax malaria: An unusual presentation

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    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.

  19. The ETRAMP family member SEP2 is expressed throughout Plasmodium berghei life cycle and is released during sporozoite gliding motility.

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    Chiara Currà

    Full Text Available The early transcribed membrane proteins ETRAMPs belong to a family of small, transmembrane molecules unique to Plasmodium parasite, which share a signal peptide followed by a short lysine-rich stretch, a transmembrane domain and a variable, highly charged C-terminal region. ETRAMPs are usually expressed in a stage-specific manner. In the blood stages they localize to the parasitophorous vacuole membrane and, in described cases, to vesicle-like structures exported to the host erythrocyte cytosol. Two family members of the rodent parasite Plasmodium berghei, uis3 and uis4, localize to secretory organelles of sporozoites and to the parasitophorous membrane vacuole of the liver stages. By the use of specific antibodies and the generation of transgenic lines, we showed that the P. berghei ETRAMP family member SEP2 is abundantly expressed in gametocytes as well as in mosquito and liver stages. In intracellular parasite stages, SEP2 is routed to the parasitophorous vacuole membrane while, in invasive ookinete and sporozoite stages, it localizes to the parasite surface. To date SEP2 is the only ETRAMP protein detected throughout the parasite life cycle. Furthermore, SEP2 is also released during gliding motility of salivary gland sporozoites. A limited number of proteins are known to be involved in this key function and the best characterized, the CSP and TRAP, are both promising transmission-blocking candidates. Our results suggest that ETRAMP members may be viewed as new potential candidates for malaria control.

  20. Protective Effect of Aqueous Crude Extract of Neem (Azadirachta indica) Leaves on Plasmodium berghei-Induced Renal Damage in Mice.

    Science.gov (United States)

    Somsak, Voravuth; Chachiyo, Sukanya; Jaihan, Ubonwan; Nakinchat, Somrudee

    2015-01-01

    Malaria is a major public health problem in the world because it can cause of death in patients. Malaria-associated renal injury is associated with 45% of mortality in adult patients hospitalized with severe form of the disease. Therefore, new plant extracts to protect against renal injury induced by malaria infection are urgently needed. In this study, we investigated the protective effect of aqueous crude extract of Azadirachta indica (neem) leaves on renal injury induced by Plasmodium berghei ANKA infection in mice. ICR mice were injected intraperitoneally with 1 × 10(7) parasitized erythrocytes of PbANKA, and neem extracts (500, 1,000, and 2,000 mg/kg) were given orally for 4 consecutive days. Plasma blood urea nitrogen (BUN) and creatinine levels were subsequently measured. Malaria-induced renal injury was evidenced as marked increases of BUN and creatinine levels. However, the oral administration of neem leaf extract to PbANKA infected mice for 4 days brought back BUN and creatinine levels to near normalcy, and the highest activity was observed at doses of 1,000 and 2,000 mg/kg. Additionally, no toxic effects were found in normal mice treated with this extract. Hence, neem leaf extract can be considered a potential candidate for protection against renal injury induced by malaria.

  1. In vivo antiplasmodial activity of extract and fractions of Trema orientalis in P. berghei-induced malaria in mice

    Institute of Scientific and Technical Information of China (English)

    Oludele Olanlokun; Moses David; Tolulope Ilori; Victoria Abe

    2016-01-01

    Objective:To assess the in vivo antimalarial potential of various solvent extracts and fractions of Trema orientalis. Methods: In this study, the animal model of antimalarial activity was employed using Plasmodium berghei-induced mice. The crude methanol extract was fractionated using vacuum liquid chromatography in the order of increasing polarity using dichloromethane, ethylacetate and methanol. Percentages of parasitemia and clearance were used as indices for antiplasmodial activities. The full blood count was also assayed while the gas chromatography-mass spectrometer analysis of the most potent fraction was carried out to detect the active compounds presenting in it. Results:Dichloromethane fraction had the least percentage of parasitemia [(0.19 ± 0.07)%] and the highest percentage of clearance [(91.74 ± 8.38)%] at the highest dose used (200 mg/kg body weight) after day 7 relative to the artemisinin control which cleared the parasite after day 3. The ethylacetate fraction showed the least percentage of clearance [(70.52 ± 5.64)%] at the highest dose used (200 mg/kg body weight) after day 7. Conclusions:The results obtained showed that purification enhanced the antiplasmodial activity of Trema orientalis in Plasmodium berghei-induced malaria in mice. The antiplasmodial activity of the dichloromethane is a strong indication that the fraction, if purified further, may contain drug candidates for the treatment of malaria in the nearest future.

  2. Hemozoin activates the innate immune system and reduces Plasmodium berghei infection in Anopheles gambiae

    OpenAIRE

    Simões, Maria L; Gonçalves, Luzia; Silveira, Henrique

    2015-01-01

    Background Malaria is a worldwide infectious disease caused by Plasmodium parasites and transmitted by female Anopheles mosquitoes. The malaria vector mosquito Anopheles can trigger effective mechanisms to control completion of the Plasmodium lifecycle; the mosquito immune response to the parasite involves several pathways which are not yet well characterized. Plasmodium metabolite hemozoin has emerged as a potent immunostimulator of mammalian tissues. In this study, we aim to investigate the...

  3. In vivo antimalarial activity of the crude root and fruit extracts of Croton macrostachyus (Euphorbiaceae) against Plasmodium berghei in mice.

    Science.gov (United States)

    Mekonnen, Laychiluh Bantie

    2015-07-01

    Euphorbiaceae (Croton macrostachyus H.; bā dòu) is used in Ethiopian folklore medicine for the treatment of malaria, gonorrhea, diabetes, wounds, fungal infections, and helminths. No scientific investigations have been performed to substantiate these claims. This study aimed to investigate the in vivo antiplasmodial activity of 80% methanol extract of the fruit and the root of Croton macrostachyus H. in a rodent model of malaria. The rodent malaria parasite Plasmodium berghei was used to inoculate healthy 8-week-old male Swiss albino mice weighing 23-27 g. Each of the hydroalcoholic crude extracts (200 mg/kg, 400 mg/kg, and 600 mg/kg) were administered to different groups of mice. The parameters of parasitemia, survival time, body weight, temperature, and packed cell volume were determined using Peter's test and Rane's test. Both extracts significantly inhibited parasitemia and increased survival time in infected mice. Maximum suppression and prolongation were obtained at the highest doses used in the study. The crude extracts prevented loss of weight and temperature, but did not affect the packed cell volume. This study suggests that the root and fruit extracts of the plant both have promising antiplasmodial activity against Plasmodium berghei in a dose-dependent manner, which supports the folkloric use of the plant for treating malaria.

  4. Serial Analysis of Gene Expression in Plasmodium berghei salivary gland sporozoites

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    Ménard Robert

    2007-12-01

    Full Text Available Abstract Background The invasion of Anopheles salivary glands by Plasmodium sporozoites is an essential step for transmission of the parasite to the vertebrate host. Salivary gland sporozoites undergo a developmental programme to express genes required for their journey from the site of the mosquito bite to the liver and subsequent invasion of, and development within, hepatocytes. A Serial Analysis of Gene Expression was performed on Anopheles gambiae salivary glands infected or not with Plasmodium berghei and we report here the analysis of the Plasmodium sporozoite transcriptome. Results Annotation of 530 tag sequences homologous to Plasmodium berghei genomic sequences identified 123 genes expressed in salivary gland sporozoites and these genes were classified according to their transcript abundance. A subset of these genes was further studied by quantitative PCR to determine their expression profiles. This revealed that sporozoites modulate their RNA amounts not only between the midgut and salivary glands, but also during their storage within the latter. Among the 123 genes, the expression of 66 is described for the first time in sporozoites of rodent Plasmodium species. Conclusion These novel sporozoite expressed genes, especially those expressed at high levels in salivary gland sporozoites, are likely to play a role in Plasmodium infectivity in the mammalian host.

  5. 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.

  6. Unlike the synchronous Plasmodium falciparum and P. chabaudi infection, the P. berghei and P. yoelii asynchronous infections are not affected by melatonin

    Directory of Open Access Journals (Sweden)

    Piero Bagnaresi

    2009-04-01

    Full Text Available Piero Bagnaresi1, Eduardo Alves1, Henrique Borges da Silva1, Sabrina Epiphanio2, Maria M Mota2, Célia RS Garcia11Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil; 2Unidade de Malária, Instituto de Medicina Molecular, Universidade de Lisboa, Lisboa, PortugalAbstract: We have previously reported that Plasmodium chabaudi and P. falciparum sense the hormone melatonin and this could be responsible for the synchrony of malaria infection. In P. chabaudi and P. falciparum, melatonin induces calcium release from internal stores, and this response is abolished by U73122, a phospholipase C inhibitor, and luzindole, a melatoninreceptor competitive antagonist. Here we show that, in vitro, melatonin is not able to modulate cell cycle, nor to elicit an elevation in intracellular calcium concentration of the intraerythrocytic forms of P. berghei or P. yoelii, two rodent parasites that show an asynchrononous development in vivo. Interestingly, melatonin and its receptor do not seem to play a role during hepatic infection by P. berghei sporozoites either. These data strengthen the hypothesis that hostderived melatonin does not synchronize malaria infection caused by P. berghei and P. yoelii. Moreover, these data explain why infections by these parasites are asynchronous, contrary to what is observed in P. falciparum and P. chabaudi infections.Keywords: malaria, calcium, melatonin, cell cycle, rhythm, sporozoite

  7. Control of Plasmodium knowlesi malaria

    Science.gov (United States)

    Abdullahi, Mohammed Baba; Hasan, Yahya Abu; Abdullah, Farah Aini

    2015-10-01

    The most significant and efficient measures against Plasmodium knowlesi outbreaks are efficient anti malaria drug, biological control in form of predatory mosquitoes and culling control strategies. In this paper optimal control theory is applied to a system of ordinary differential equation. It describes the disease transmission and Pontryagin's Maximum Principle is applied for analysis of the control. To this end, three control strategies representing biological control, culling and treatment were incorporated into the disease transmission model. The simulation results show that the implementation of the combination strategy during the epidemic is the most cost-effective strategy for disease transmission.

  8. Effects of the methanolic seeds extract of Carica Papaya on plasmodium Berghei infected mice

    Institute of Scientific and Technical Information of China (English)

    Amazu LU; Ebong OO; Azikiwe CCA; Unekwe PC; Siminialayi MI; Nwosu PJC; Ezeani MC; Obidiya OS; Ajugwo AO

    2009-01-01

    into 5subgroups (a-e)of 5animals per group.At the appropriate time,50 mg/kg/day,1 00 mg/kg/day and 200 mg/kg/day of crude extract of C.papaya were administered orally to the different subgroups(b-d)within the three main groups.One subgroup(a)in each main group also received orally,5 mg/kg/day of chloroquine phosphate as positive control while one subgroup (e)in each main group also received orally,0.2 mL /kg/day of distilled water as negative control.Malaria parasites infected red blood cells numbering 1 ×1 07 and suspended in 0.2 mL of physiological saline was inoc-ulated intraperitoneally,to each animal of the subgroups (a-d)in each of the three main groups at the appro-priate time.Blood smears were made from animals'tail,stained with Lieshman and examined microscopically at 100 ×for the presence of malaria parasite.Percentage malaria parastaemia was calculated as well as average percentage malaria parasitaemia suppression.Results:Extraction yield of 25.29% was obtained while the LD50 was 620 mg/kg.The phytochemistry showed the richly presence of alkaloids,as well as glycosides,car-bohydrates,resins,fats and fixed oils.The suppressive study at doses of 200,100 and 50mg/kg/day showed 53.02%,43.43% and 19.83 % suppressive activity against Plasmodium berghei respectively.This activity compared to that of chloroquine,a standard antimalaria drug that gave 95.95% suppressive anti-parasitaemia. The prophylactic study at doses of 200,100 and 50 mg/kg/day showed 63.85%,61.12% and 48.08% pre-vention to malaria parasitaemia respectively as against 94.78% showed by chloroquine.The curative study however,at doses of 200,100 and 50 mg/kg/day failed to suppress malaria parasitaemia with a mean survival range of 6-8days as against 27.2 days showed by chloroquine.The seeds extract of C.papaya showed a signifi-cant malaria parasitaemia suppressive activity (P≤0.05).These activities are dose dependent and compara-ble to those of Chloroquine phosphate.Conclusion:The results above

  9. Curcumin-arteether combination therapy of Plasmodium berghei-infected mice prevents recrudescence through immunomodulation.

    Directory of Open Access Journals (Sweden)

    Palakkod G Vathsala

    Full Text Available Earlier studies in this laboratory have shown the potential of artemisinin-curcumin combination therapy in experimental malaria. In a parasite recrudescence model in mice infected with Plasmodium berghei (ANKA, a single dose of alpha,beta-arteether (ART with three oral doses of curcumin prevented recrudescence, providing almost 95% protection. The parasites were completely cleared in blood with ART-alone (AE or ART+curcumin (AC treatments in the short-term, although the clearance was faster in the latter case involving increased ROS generation. But, parasites in liver and spleen were not cleared in AE or AC treatments, perhaps, serving as a reservoir for recrudescence. Parasitemia in blood reached up to 60% in AE-treated mice during the recrudescence phase, leading to death of animals. A transient increase of up to 2-3% parasitemia was observed in AC-treatment, leading to protection and reversal of splenomegaly. A striking increase in spleen mRNA levels for TLR2, IL-10 and IgG-subclass antibodies but a decrease in those for INFγ and IL-12 was observed in AC-treatment. There was a striking increase in IL-10 and IgG subclass antibody levels but a decrease in INFγ levels in sera leading to protection against recrudescence. AC-treatment failed to protect against recrudescence in TLR2(-/- and IL-10(-/- animals. IL-10 injection to AE-treated wild type mice and AC-treated TLR2(-/- mice was able to prolong survival. Blood from the recrudescence phase in AE-treatment, but not from AC-treatment, was able to reinfect and kill naïve animals. Sera from the recrudescence phase of AC-treated animals reacted with several parasite proteins compared to that from AE-treated animals. It is proposed that activation of TLR2-mediated innate immune response leading to enhanced IL-10 production and generation of anti-parasite antibodies contribute to protective immunity in AC-treated mice. These results indicate a potential for curcumin-based combination therapy to

  10. Plasmodium berghei calcium dependent protein kinase 1 is not required for host cell invasion.

    Science.gov (United States)

    Jebiwott, Sylvia; Govindaswamy, Kavitha; Mbugua, Amos; Bhanot, Purnima

    2013-01-01

    Plasmodium Calcium Dependent Protein Kinase (CDPK1) is required for the development of sexual stages in the mosquito. In addition, it is proposed to play an essential role in the parasite's invasive stages possibly through the regulation of the actinomyosin motor and micronemal secretion. We demonstrate that Plasmodium berghei CDPK1 is dispensable in the parasite's erythrocytic and pre-erythrocytic stages. We successfully disrupted P. berghei CDPK1 (PbCDPK1) by homologous recombination. The recovery of erythrocytic stage parasites lacking PbCDPK1 (PbCDPK1-) demonstrated that PbCDPK1 is not essential for erythrocytic invasion or intra-erythrocytic development. To study PbCDPK1's role in sporozoites and liver stage parasites, we generated a conditional mutant (CDPK1 cKO). Phenotypic characterization of CDPK1 cKO sporozoites demonstrated that CDPK1 is redundant or dispensable for the invasion of mammalian hepatocytes, the egress of parasites from infected hepatocytes and through the subsequent erythrocytic cycle. We conclude that P. berghei CDPK1 plays an essential role only in the mosquito sexual stages.

  11. Plasmodium berghei calcium dependent protein kinase 1 is not required for host cell invasion.

    Directory of Open Access Journals (Sweden)

    Sylvia Jebiwott

    Full Text Available Plasmodium Calcium Dependent Protein Kinase (CDPK1 is required for the development of sexual stages in the mosquito. In addition, it is proposed to play an essential role in the parasite's invasive stages possibly through the regulation of the actinomyosin motor and micronemal secretion. We demonstrate that Plasmodium berghei CDPK1 is dispensable in the parasite's erythrocytic and pre-erythrocytic stages. We successfully disrupted P. berghei CDPK1 (PbCDPK1 by homologous recombination. The recovery of erythrocytic stage parasites lacking PbCDPK1 (PbCDPK1- demonstrated that PbCDPK1 is not essential for erythrocytic invasion or intra-erythrocytic development. To study PbCDPK1's role in sporozoites and liver stage parasites, we generated a conditional mutant (CDPK1 cKO. Phenotypic characterization of CDPK1 cKO sporozoites demonstrated that CDPK1 is redundant or dispensable for the invasion of mammalian hepatocytes, the egress of parasites from infected hepatocytes and through the subsequent erythrocytic cycle. We conclude that P. berghei CDPK1 plays an essential role only in the mosquito sexual stages.

  12. Plasmodium falciparum malaria associated with ABO blood ...

    African Journals Online (AJOL)

    Plasmodium falciparum malaria associated with ABO blood phenotypes and ... out to investigate the relationship between blood group types and P. falciparum ... of long lasting treated (LLT) mosquito bed nets and the prevalence of infection.

  13. Translational repression of the cpw-wpc gene family in the malaria parasite Plasmodium

    KAUST Repository

    Rao, Pavitra N.

    2016-06-14

    The technical challenges of working with the sexual stages of the malaria parasite Plasmodium have hindered the characterization of sexual stage antigens in the quest for a successful malaria transmission-blocking vaccine. One such predicted and largely uncharacterized group of sexual stage candidate antigens is the CPW-WPC family of proteins. CPW-WPC proteins are named for a characteristic domain that contains two conserved motifs, CPxxW and WPC. Conserved across Apicomplexa, this family is also present earlier in the Alveolata in the free-living, non-parasitophorous, photosynthetic chromerids, Chromera and Vitrella. In P. falciparum and P. berghei blood stage parasites the transcripts of all nine cpw-wpc genes have been detected in gametocytes. RNA immunoprecipitation followed by reverse transcriptase-PCR reveals all P. berghei cpw-wpc transcripts to be bound by the translational repressors DOZI and CITH, and thus are likely under translational control prior to transmission from the rodent host to the mosquito vector in P. berghei. The GFP tagging of two endogenous P. berghei genes confirmed translational silencing in the gametocyte and translation in ookinetes. Establishing a luciferase transgene assay we show that the 3′ untranslated region of PF3D7_1331400 controls protein expression of this reporter in P. falciparum gametocytes. Our analyses suggest that cpw-wpc genes are translationally silenced in gametocytes across Plasmodium spp. and activated during ookinete formation and thus may have a role in transmission to the mosquito.

  14. Apoptosis of erythrocytic stage parasites of Plasmodium berghei chloroquine-resistant strain

    Institute of Scientific and Technical Information of China (English)

    CHEN Ke-qiang; SONG Guan-hong

    2002-01-01

    Objective: To explore the characteristics of crisis state at erythrocytic stage of Plasmodium berghei chloroquine-resistant (RC) strain. Methods: Agarose electrophoresis, optical and transmission electron microscopes were used. Patterns of genomic DNA structures and ultra-structures of the erythrocytic parasites were observed in ICA mice (infected with the RC strain) during rising and declining of parasitemia. Results: During the declining parasitemia, the erythrocytic stage parasites of the RC strain showed round or oval appearance with intact plasma membrane and shrank nuclei with no metabolic window, mitochondria or other membranaceous structures. Their DNA electrophoretogram revealed a ladder pattern which evidently differed from the parasites of the RC strain in the rising parasitemia and the chloroquine-sensitive (N) strain.Conclusion: The crisis state of the erythrocytic stage parasites of the P. berghei chloroquine-resistant (RC)strain is characterized by apoptosis.

  15. Development of an in vitro assay and demonstration of Plasmodium berghei liver-stage inhibition by TRAP-specific CD8+ T cells.

    Directory of Open Access Journals (Sweden)

    Rhea J Longley

    Full Text Available The development of an efficacious vaccine against the Plasmodium parasite remains a top priority. Previous research has demonstrated the ability of a prime-boost virally vectored sub-unit vaccination regimen, delivering the liver-stage expressed malaria antigen TRAP, to produce high levels of antigen-specific T cells. The liver-stage of malaria is the main target of T cell-mediated immunity, yet a major challenge in assessing new T cell inducing vaccines has been the lack of a suitable pre-clinical assay. We have developed a flow-cytometry based in vitro T cell killing assay using a mouse hepatoma cell line, Hepa1-6, and Plasmodium berghei GFP expressing sporozoites. Using this assay, P. berghei TRAP-specific CD8+ T cell enriched splenocytes were shown to inhibit liver-stage parasites in an effector-to-target ratio dependent manner. Further development of this assay using human hepatocytes and P. falciparum would provide a new method to pre-clinically screen vaccine candidates and to elucidate mechanisms of protection in vitro.

  16. Activation and exhaustion of antigen-specific CD8(+) T cells occur in different splenic compartments during infection with Plasmodium berghei.

    Science.gov (United States)

    Bayarsaikhan, Ganchimeg; Miyakoda, Mana; Yamamoto, Kazuo; Kimura, Daisuke; Akbari, Masoud; Yuda, Masao; Yui, Katsuyuki

    2017-06-01

    The spleen is the major organ in which T cells are primed during infection with malaria parasites. However, little is known regarding the dynamics of the immune responses and their localization within the splenic tissue during malaria infection. We examined murine CD8(+) T cell responses during infection with Plasmodium berghei using recombinant parasites expressing a model antigen ovalbumin (OVA) protein and compared the responses with those elicited by Listeria monocytogenes expressing the same antigen. OVA-specific CD8(+) T cells were mainly activated in the white pulp of the spleen during malaria infection, as similarly observed during Listeria infection. However, the fates of these activated CD8(+) T cells were distinct. During infection with malaria parasites, activated CD8(+) T cells preferentially accumulated in the red pulp and/or marginal zone, where cytokine production of OVA-specific CD8(+) T cells decreased, and the expression of multiple inhibitory receptors increased. These cells preferentially underwent apoptosis, suggesting that T cell exhaustion mainly occurred in the red pulp and/or marginal zone. However, during Listeria infection, OVA-specific CD8(+) T cells only transiently expressed inhibitory receptors in the white pulp and maintained their ability to produce cytokines and become memory cells. These results highlighted the distinct fates of CD8(+) T cells during infection with Plasmodium parasites and Listeria, and suggested that activation and exhaustion of specific CD8(+) T cells occurred in distinct spleen compartments during infection with malaria parasites.

  17. Plasmodium falciparum Malaria, Southern Algeria, 2007

    OpenAIRE

    Boubidi, Saïd C; Gassen, Ibrahim; Khechache, Yacine; Lamali, Karima; Tchicha, Boualem; Brengues, Cécile; Menegon, Michela; Severini, Carlo; Fontenille, Didier; Harrat, Zoubir

    2010-01-01

    An outbreak of Plasmodium falciparum malaria occurred in Tinzaouatine in southern Algeria in 2007. The likely vector, Anopheles gambiae mosquitoes, had not been detected in Algeria. Genes for resistance to chloroquine were detected in the parasite. The outbreak shows the potential for an increase in malaria vectors in Algeria.

  18. Congenital Plasmodium falciparum Malaria in Washington, DC.

    Science.gov (United States)

    Del Castillo, Melissa; Szymanski, Ann Marie; Slovin, Ariella; Wong, Edward C C; DeBiasi, Roberta L

    2017-01-11

    Congenital malaria is rare in the United States, but is an important diagnosis to consider when evaluating febrile infants. Herein, we describe a case of congenital Plasmodium falciparum malaria in a 2-week-old infant born in the United States to a mother who had emigrated from Nigeria 3 months before delivery. © The American Society of Tropical Medicine and Hygiene.

  19. Plasmodium falciparum Malaria, Southern Algeria, 2007

    Science.gov (United States)

    Gassen, Ibrahim; Khechache, Yacine; Lamali, Karima; Tchicha, Boualem; Brengues, Cécile; Menegon, Michela; Severini, Carlo; Fontenille, Didier; Harrat, Zoubir

    2010-01-01

    An outbreak of Plasmodium falciparum malaria occurred in Tinzaouatine in southern Algeria in 2007. The likely vector, Anopheles gambiae mosquitoes, had not been detected in Algeria. Genes for resistance to chloroquine were detected in the parasite. The outbreak shows the potential for an increase in malaria vectors in Algeria. PMID:20113565

  20. Plasmodium falciparum Malaria, Southern Algeria, 2007

    OpenAIRE

    Boubidi, Saïd C; Gassen, Ibrahim; Khechache, Yacine; Lamali, Karima; Tchicha, Boualem; Brengues, Cécile; Menegon, Michela; Severini, Carlo; Fontenille, Didier; Harrat, Zoubir

    2010-01-01

    An outbreak of Plasmodium falciparum malaria occurred in Tinzaouatine in southern Algeria in 2007. The likely vector, Anopheles gambiae mosquitoes, had not been detected in Algeria. Genes for resistance to chloroquine were detected in the parasite. The outbreak shows the potential for an increase in malaria vectors in Algeria.

  1. Bioinformatics analysis and prediction for structure and function of nitric oxide synthase and similar proteins from Plasmodium berghei

    Institute of Scientific and Technical Information of China (English)

    Zhigang Fan; Gang Lv; Lingmin Zhang; Xiufeng Gan; Qiang Wu; Saifeng Zhong; Guogang Yan; Guifen Lin

    2011-01-01

    Objective: To search and analyze nitric oxide synthase (NOS) and similar proteins fromPlasmodium berghei(Pb). Methods: The structure and function of nitric oxide synthase and similar proteins from Plasmodium berghei were analyzed and predicted by bioinformatics. Results: PbNOS were not available, but nicotinamide adenine dinucleotide 2’-phosphate reduced tetrasodium (NADPH)-cytochrome p450 reductase(CPR) were gained. PbCPR was in the nucleus of Plasmodium berghei, while 134aa-229aa domain was localize in nucleolar organizer. The amino acids sequence of PbCPR had the closest genetic relationship with Plasmodium vivax showing a 73% homology. The tertiary structure of PbCPR displayed the forcep-shape with wings, but no wings existed in the tertiary structure of its’ host, Mus musculus(Mm). 137aa-200aa, 201aa-218aa, 220aa-230aa, 232aa-248, 269aa-323aa, 478aa-501aa and 592aa-606aa domains of PbCPR showed no homology with MmCPRs’, and all domains were exposed on the surface of the protein. Conclusions: NOS can’t be found in Plasmodium berghei and other Plasmodium species. PbCPR may be a possible resistance site of antimalarial drug, and the targets of antimalarial drug and vaccine. It may be also one of the mechanisms of immune evasion. This study on Plasmodium berghei may be more suitable to Plasmodium vivax. And137aa-200aa, 201aa-218aa, 220aa-230aa, 232aa-248, 269aa-323aa, 478aa-501aa and 592aa-606aa domains ofPb CPR are more ideal targets of antimalarial drug and vaccine.

  2. Quantitative real-time PCR analysis of Anopheles dirus TEP1 and NOS during Plasmodium berghei infection, using three reference genes

    Directory of Open Access Journals (Sweden)

    Jonathan W.K. Liew

    2017-07-01

    Full Text Available Quantitative reverse transcription PCR (qRT-PCR has been an integral part of characterizing the immunity of Anopheles mosquitoes towards Plasmodium invasion. Two anti-Plasmodium factors of Anopheles, thioester-containing protein 1 (TEP1 and nitric oxide synthase (NOS, play a role in the refractoriness of Anopheles towards Plasmodium infection and are generally expressed during infection. However, these are less studied in Anopheles dirus, a dominant malaria vector in Southeast Asia. Furthermore, most studies used a single reference gene for normalization during gene expression analysis without proper validation. This may lead to erroneous quantification of expression levels. Therefore, the present study characterized and investigated the expression profiles of TEP1 and NOS of Anopheles dirus during P. berghei infection. Prior to that, the elongation factor 1-alpha (EF1, actin 1 (Act and ribosomal protein S7 (S7 genes were validated for their suitability as a set of reference genes. TEP1 and NOS expressions in An. dirus were found to be significantly induced after P. berghei infection.

  3. In vivo antimalarial activity of leaves of Plectranthus amboinicus (lour) spreng on Plasmodium berghei yoelii.

    Science.gov (United States)

    Periyanayagam, K; Nirmala Devi, K; Suseela, L; Uma, A; Ismail, M

    2008-06-01

    An invivo study of aqueous extract of the leaves of Plectranthus amboinicus on Plasmodium berghei yoelii was conducted on laboratory infected albino mice and compared with standard drug chloroquine. Reduction of parasitemia at 250 mg/kg and 500 mg/kg of aqueous extract for 24 hrs, 48 hrs, 72 hrs and 96 hrs were determined. The reduction of parasitemia after 96 hrs was 100%, 67.9% and 76.2% for standard, 250 mg/kg and 500 mg/kg of aqueous extract respectively. The isolation of active principle responsible for the reduction of parasitemia may give a promising drug molecule.

  4. Improved negative selection protocol for Plasmodium berghei in the rodent malarial model

    Directory of Open Access Journals (Sweden)

    Orr Rachael Y

    2012-03-01

    Full Text Available Abstract An improved methodology is presented here for transgenic Plasmodium berghei lines that express the negative selectable marker yFCU (a bifunctional protein that combines yeast cytosine deaminase and uridyl phosphoribosyl transferase (UPRT and substitutes delivery of selection drug 5-fluorocytosine (5FC by intraperitoneal injection for administration via the drinking water of the mice. The improved methodology is shown to be as effective, less labour-intensive, reduces animal handling and animal numbers required for successful selection thereby contributing to two of the "three Rs" of animal experimentation, namely refinement and reduction.

  5. 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.

  6. Anopheles gambiae eicosanoids modulate Plasmodium berghei survival from oocyst to salivary gland invasion

    Directory of Open Access Journals (Sweden)

    Susana Ramos

    2014-08-01

    Full Text Available Eicosanoids affect the immunity of several pathogen/insect models, but their role on the Anopheles gambiae response to Plasmodium is still unknown. Plasmodium berghei-infected mosquitoes were injected with an eicosanoid biosynthesis inhibitor, indomethacin (IN, or a substrate, arachidonic acid (AA, at day 7 or day 12 post-infection (p.i.. Salivary gland invasion was evaluated by sporozoite counts at day 21 p.i. IN promoted infection upon sporozoite release from oocysts, but inhibited infection when sporozoites were still maturing within the oocysts, as observed by a reduction in the number of sporozoites reaching the salivary glands. AA treatment had the opposite effect. We show for the first time that An. gambiae can modulate parasite survival through eicosanoids by exerting an antagonistic or agonistic effect on the parasite, depending on its stage of development.

  7. Anopheles gambiae eicosanoids modulate Plasmodium berghei survival from oocyst to salivary gland invasion.

    Science.gov (United States)

    Ramos, Susana; Custódio, Ana; Silveira, Henrique

    2014-08-01

    Eicosanoids affect the immunity of several pathogen/insect models, but their role on the Anopheles gambiae response to Plasmodium is still unknown. Plasmodium berghei-infected mosquitoes were injected with an eicosanoid biosynthesis inhibitor, indomethacin (IN), or a substrate, arachidonic acid (AA), at day 7 or day 12 post-infection (p.i.). Salivary gland invasion was evaluated by sporozoite counts at day 21 p.i. IN promoted infection upon sporozoite release from oocysts, but inhibited infection when sporozoites were still maturing within the oocysts, as observed by a reduction in the number of sporozoites reaching the salivary glands. AA treatment had the opposite effect. We show for the first time that An. gambiae can modulate parasite survival through eicosanoids by exerting an antagonistic or agonistic effect on the parasite, depending on its stage of development.

  8. A cysteine protease inhibitor of plasmodium berghei is essential for exo-erythrocytic development.

    Directory of Open Access Journals (Sweden)

    Christine Lehmann

    2014-08-01

    Full Text Available Plasmodium parasites express a potent inhibitor of cysteine proteases (ICP throughout their life cycle. To analyze the role of ICP in different life cycle stages, we generated a stage-specific knockout of the Plasmodium berghei ICP (PbICP. Excision of the pbicb gene occurred in infective sporozoites and resulted in impaired sporozoite invasion of hepatocytes, despite residual PbICP protein being detectable in sporozoites. The vast majority of these parasites invading a cultured hepatocyte cell line did not develop to mature liver stages, but the few that successfully developed hepatic merozoites were able to initiate a blood stage infection in mice. These blood stage parasites, now completely lacking PbICP, exhibited an attenuated phenotype but were able to infect mosquitoes and develop to the oocyst stage. However, PbICP-negative sporozoites liberated from oocysts exhibited defective motility and invaded mosquito salivary glands in low numbers. They were also unable to invade hepatocytes, confirming that control of cysteine protease activity is of critical importance for sporozoites. Importantly, transfection of PbICP-knockout parasites with a pbicp-gfp construct fully reversed these defects. Taken together, in P. berghei this inhibitor of the ICP family is essential for sporozoite motility but also appears to play a role during parasite development in hepatocytes and erythrocytes.

  9. Identification and bioinformatic characterization of a multidrug resistance associated protein (ABCC) gene in Plasmodium berghei

    Science.gov (United States)

    González-Pons, María; Szeto, Ada C; González-Méndez, Ricardo; Serrano, Adelfa E

    2009-01-01

    Background The ATP-binding cassette (ABC) superfamily is one of the largest evolutionarily conserved families of proteins. ABC proteins play key roles in cellular detoxification of endobiotics and xenobiotics. Overexpression of certain ABC proteins, among them the multidrug resistance associated protein (MRP), contributes to drug resistance in organisms ranging from human neoplastic cells to parasitic protozoa. In the present study, the Plasmodium berghei mrp gene (pbmrp) was partially characterized and the predicted protein was classified using bioinformatics in order to explore its putative involvement in drug resistance. Methods The pbmrp gene from the P. berghei drug sensitive, N clone, was sequenced using a PCR strategy. Classification and domain organization of pbMRP were determined with bioinformatics. The Plasmodium spp. MRPs were aligned and analysed to study their conserved motifs and organization. Gene copy number and organization were determined via Southern blot analysis in both N clone and the chloroquine selected line, RC. Chromosomal Southern blots and RNase protection assays were employed to determine the chromosomal location and expression levels of pbmrp in blood stages. Results The pbmrp gene is a single copy, intronless gene with a predicted open reading frame spanning 5820 nucleotides. Bioinformatic analyses show that this protein has distinctive features characteristic of the ABCC sub-family. Multiple sequence alignments reveal a high degree of conservation in the nucleotide binding and transmembrane domains within the MRPs from the Plasmodium spp. analysed. Expression of pbmrp was detected in asexual blood stages. Gene organization, copy number and mRNA expression was similar in both lines studied. A chromosomal translocation was observed in the chloroquine selected RC line, from chromosome 13/14 to chromosome 8, when compared to the drug sensitive N clone. Conclusion In this study, the pbmrp gene was sequenced and classified as a member of

  10. Epidemiology of Plasmodium vivax Malaria in India.

    Science.gov (United States)

    Anvikar, Anupkumar R; Shah, Naman; Dhariwal, Akshay C; Sonal, Gagan Singh; Pradhan, Madan Mohan; Ghosh, Susanta K; Valecha, Neena

    2016-12-28

    Historically, malaria in India was predominantly caused by Plasmodium vivax, accounting for 53% of the estimated cases. After the spread of drug-resistant Plasmodium falciparum in the 1990s, the prevalence of the two species remained equivalent at the national level for a decade. By 2014, the proportion of P. vivax has decreased to 34% nationally, but with high regional variation. In 2014, P. vivax accounted for around 380,000 malaria cases in India; almost a sixth of all P. vivax cases reported globally. Plasmodium vivax has remained resistant to control measures, particularly in urban areas. Urban malaria is predominantly caused by P. vivax and is subject to outbreaks, often associated with increased mortality, and triggered by bursts of migration and construction. The epidemiology of P. vivax varies substantially within India, including multiple relapse phenotypes with varying latencies between primary infection and relapse. Moreover, the hypnozoite reservoir maintains transmission potential and enables reestablishment of the parasite in areas in which it was thought eradicated. The burden of malaria in India is complex because of the highly variable malaria eco-epidemiological profiles, transmission factors, and the presence of multiple Plasmodium species and Anopheles vectors. This review of P. vivax malaria in India describes epidemiological trends with particular attention to four states: Gujarat, Karnataka, Haryana, and Odisha.

  11. Transgenic malaria-resistant mosquitoes have a fitness advantage when feeding on Plasmodium-infected blood.

    Science.gov (United States)

    Marrelli, Mauro T; Li, Chaoyang; Rasgon, Jason L; Jacobs-Lorena, Marcelo

    2007-03-27

    The introduction of genes that impair Plasmodium development into mosquito populations is a strategy being considered for malaria control. The effect of the transgene on mosquito fitness is a crucial parameter influencing the success of this approach. We have previously shown that anopheline mosquitoes expressing the SM1 peptide in the midgut lumen are impaired for transmission of Plasmodium berghei. Moreover, the transgenic mosquitoes had no noticeable fitness load compared with nontransgenic mosquitoes when fed on noninfected mice. Here we show that when fed on mice infected with P. berghei, these transgenic mosquitoes are more fit (higher fecundity and lower mortality) than sibling nontransgenic mosquitoes. In cage experiments, transgenic mosquitoes gradually replaced nontransgenics when mosquitoes were maintained on mice infected with gametocyte-producing parasites (strain ANKA 2.34) but not when maintained on mice infected with gametocyte-deficient parasites (strain ANKA 2.33). These findings suggest that when feeding on Plasmodium-infected blood, transgenic malaria-resistant mosquitoes have a selective advantage over nontransgenic mosquitoes. This fitness advantage has important implications for devising malaria control strategies by means of genetic modification of mosquitoes.

  12. Epidemiology of Plasmodium vivax Malaria in India

    OpenAIRE

    Anvikar, Anupkumar R; Shah, Naman; Dhariwal, Akshay C.; Sonal, Gagan Singh; Pradhan, Madan Mohan; Ghosh, Susanta K; Valecha, Neena

    2016-01-01

    Historically, malaria in India was predominantly caused by Plasmodium vivax, accounting for 53% of the estimated cases. After the spread of drug-resistant Plasmodium falciparum in the 1990s, the prevalence of the two species remained equivalent at the national level for a decade. By 2014, the proportion of P. vivax has decreased to 34% nationally, but with high regional variation. In 2014, P. vivax accounted for around 380,000 malaria cases in India; almost a sixth of all P. vivax cases repor...

  13. The alveolin IMC1h is required for normal ookinete and sporozoite motility behaviour and host colonisation in Plasmodium berghei.

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    Katrin Volkmann

    Full Text Available Alveolins, or inner membrane complex (IMC proteins, are components of the subpellicular network that forms a structural part of the pellicle of malaria parasites. In Plasmodium berghei, deletions of three alveolins, IMC1a, b, and h, each resulted in reduced mechanical strength and gliding velocity of ookinetes or sporozoites. Using time lapse imaging, we show here that deletion of IMC1h (PBANKA_143660 also has an impact on the directionality and motility behaviour of both ookinetes and sporozoites. Despite their marked motility defects, sporozoites lacking IMC1h were able to invade mosquito salivary glands, allowing us to investigate the role of IMC1h in colonisation of the mammalian host. We show that IMC1h is essential for sporozoites to progress through the dermis in vivo but does not play a significant role in hepatoma cell transmigration and invasion in vitro. Colocalisation of IMC1h with the residual IMC in liver stages was detected up to 30 hours after infection and parasites lacking IMC1h showed developmental defects in vitro and a delayed onset of blood stage infection in vivo. Together, these results suggest that IMC1h is involved in maintaining the cellular architecture which supports normal motility behaviour, access of the sporozoites to the blood stream, and further colonisation of the mammalian host.

  14. The alveolin IMC1h is required for normal ookinete and sporozoite motility behaviour and host colonisation in Plasmodium berghei.

    Science.gov (United States)

    Volkmann, Katrin; Pfander, Claudia; Burstroem, Charlotte; Ahras, Malika; Goulding, David; Rayner, Julian C; Frischknecht, Friedrich; Billker, Oliver; Brochet, Mathieu

    2012-01-01

    Alveolins, or inner membrane complex (IMC) proteins, are components of the subpellicular network that forms a structural part of the pellicle of malaria parasites. In Plasmodium berghei, deletions of three alveolins, IMC1a, b, and h, each resulted in reduced mechanical strength and gliding velocity of ookinetes or sporozoites. Using time lapse imaging, we show here that deletion of IMC1h (PBANKA_143660) also has an impact on the directionality and motility behaviour of both ookinetes and sporozoites. Despite their marked motility defects, sporozoites lacking IMC1h were able to invade mosquito salivary glands, allowing us to investigate the role of IMC1h in colonisation of the mammalian host. We show that IMC1h is essential for sporozoites to progress through the dermis in vivo but does not play a significant role in hepatoma cell transmigration and invasion in vitro. Colocalisation of IMC1h with the residual IMC in liver stages was detected up to 30 hours after infection and parasites lacking IMC1h showed developmental defects in vitro and a delayed onset of blood stage infection in vivo. Together, these results suggest that IMC1h is involved in maintaining the cellular architecture which supports normal motility behaviour, access of the sporozoites to the blood stream, and further colonisation of the mammalian host.

  15. Virus-Like Particle (VLP Plus Microcrystalline Tyrosine (MCT Adjuvants Enhance Vaccine Efficacy Improving T and B Cell Immunogenicity and Protection against Plasmodium berghei/vivax

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    Gustavo Cabral-Miranda

    2017-05-01

    Full Text Available Vaccination is the most effective prophylactic tool against infectious diseases. Despite continued efforts to control malaria, the disease still generally represents a significant unmet medical need. Microcrystalline tyrosine (MCT is a well described depot used in licensed allergy immunotherapy products and in clinical development. However, its proof of concept in prophylactic vaccines has only recently been explored. MCT has never been used in combination with virus-like particles (VLPs, which are considered to be one of the most potent inducers of cellular and humoral immune responses in mice and humans. In the current study we assessed the potential of MCT to serve as an adjuvant in the development of a vaccine against malaria either alone or combined with VLP using Plasmodium vivax thrombospondin-related adhesive protein (TRAP as a target antigen. We chemically coupled PvTRAP to VLPs derived from the cucumber mosaic virus fused to a universal T-cell epitope of the tetanus toxin (CMVtt, formulated with MCT and compared the induced immune responses to PvTRAP formulated in PBS or Alum. The protective capacity of the various formulations was assessed using Plasmodium berghei expressing PvTRAP. All vaccine formulations using adjuvants and/or VLP increased humoral immunogenicity for PvTRAP compared to the antigen alone. The most proficient responder was the group of mice immunized with the vaccine formulated with PvTRAP-VLP + MCT. The VLP-based vaccine formulated in MCT also induced the strongest T cell response and conferred best protection against challenge with recombinant Plasmodium berghei. Thus, the combination of VLP with MCT may take advantage of the properties of each component and appears to be an alternative biodegradable depot adjuvant for development of novel prophylactic vaccines.

  16. C3d-defined complement receptor-binding peptide p28 conjugated to circumsporozoite protein provides protection against Plasmodium berghei.

    Science.gov (United States)

    Bergmann-Leitner, Elke S; Duncan, Elizabeth H; Leitner, Wolfgang W; Neutzner, Albert; Savranskaya, Tatyana; Angov, Evelina; Tsokos, George C

    2007-11-01

    Immune response against circumsporozoite protein (CSP) of Plasmodium berghei, a major surface protein on the sporozoite, confers protection in various murine malaria models. Engineered DNA vaccine encoding CSP and 3 copies of C3d caused an unexpected loss in protection attributed to the binding of C3d to the C-terminal region of CSP. Because the C3d region known as p28 represents the complement receptor (CR) 2-binding motif, we developed a CSP-3 copies of p28 DNA construct (CSP-3p28). CSP-3p28-immunized mice were better protected against P. berghei sporozoites than CSP-immunized mice 6 weeks after the 2nd boost, produced sufficient IgG1 anti-CSP and CSP C-terminus antibody and failed to produce IgG2a. CSP-3C3d-immunized mice were not protected, failed to produce IgG1 and produced high amounts of IgG2a. We conclude that use of the CR2-binding motif of C3d as molecular adjuvant to CSP results in anti-malaria protective immune response probably by targeting the chimeric protein to CR2.

  17. Efeito do Mycobacterium bovis BCG, lipopolissacarideo bacteriano e hidrocortisona no desenvolvimento de imunidade ao Plasmodium berghei em camundongos

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    José J. Ferraroni

    1986-02-01

    Full Text Available Mycobacterium bovis (BCG aumenta significantemente o desenvolvimento da imunidade nos camundongos CFW, C57BL/6, C57BL/l0ScN e BALB/c (Nu/+ para os estágios eritrocitos do Plasmodium berghei. Camundongos tratados com BCG requerem menos ciclos de infecção com P. berghei e cura pelo Fansidar (pirimetamina + sulfadoxina para desenvolverem imunidade sólida a este parasita do que os controles. Contudo, os animais que receberam BCG 30 dias antes do início da imunização evidenciaram uma perda precoce da imunidade adquirida para o P. berghei, quando comparado com os animais que receberam BCG 14 dias antes ou que não receberam BCG. Assim, sendo, o BCG aumentada a indução na resposta imune do hospedeiro ao P. berghei no curso de infecções subseqüentes. O tratamento de camundongos CFW, BALB/c e C57BL/6 com lipopolissacarídeo bacteriano ou hidrocortisona faz com que os animais requeiram um número maior de ciclos de infecção e cura para tornarem-se imunes ao P. berghei que os controles. O tratamento dos camundongos C57BL/10ScN com hidrocortisona aboliu completamente a sua habilidade de sobrevida subseqüentes a ciclos de infecção com P. berghei e cura pelo Fansidar.

  18. Prevalence of Malaria Plasmodium in Abeokuta, Nigeria

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    Okonko, I. O.

    2009-01-01

    Full Text Available This study reports the prevalence of malaria caused by plasmodium between genders in Abeokuta, the capital city of Ogun State located in the forest zone of southwestern Nigeria between January 2002 and December 2004. Blood film examination for malaria parasites in 708 patients; 366 males and 342 females. Microscopic examination of thick films techniques was employed for this study. Of the 708 (100% patients examined, 577 (81.5% were Plasmodium-positive. A high malaria parasite prevalence rate of 81.5% was noted in this study. Female subjects were more infected (42.4% than males (41.9% however, there was no significant difference in the sex of the subjects studied (p=0.05. A high malaria parasite prevalence rate of 86.9% was noted in samples collected in year 2003 than in other years studied. There was significant difference in the years under study (p=0.05. This study shows that a good percentage of people were infested by malaria Plasmodium. This could be attributed to lack of adequate accommodation and poor sanitary conditions in the area under study. Although several efforts have been made to effectively control the high incidence of malaria in Nigeria, these have been largely unsuccessful due to a number of reasons such as irrigated urban agriculture which can be the malaria vector’s breeding ground in the city, stagnant gutters and swamps in our environment where mosquitoes breed in millions, and lack of political will and commitment of the government in its disease management program, low awareness of the magnitude of malaria problem, poor health practices by individuals and communities and resistance to drugs. Therefore, future interventions in Nigeria should be directed toward controlling malaria in the context of a moderate transmission setting; thus, large-scale distribution of insecticide-treated nets or widespread use of indoor residual spraying may be less cost-effective than enhanced surveillance with effective case management or

  19. Study of the antimalarial properties of hydroxyethylamine derivatives using green fluorescent protein transformed Plasmodium berghei

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    Mariana Conceição Souza

    2015-06-01

    Full Text Available A rapid decrease in parasitaemia remains the major goal for new antimalarial drugs and thus, in vivo models must provide precise results concerning parasitaemia modulation. Hydroxyethylamine comprise an important group of alkanolamine compounds that exhibit pharmacological properties as proteases inhibitors that has already been proposed as a new class of antimalarial drugs. Herein, it was tested the antimalarial property of new nine different hydroxyethylamine derivatives using the green fluorescent protein (GFP-expressing Plasmodium berghei strain. By comparing flow cytometry and microscopic analysis to evaluate parasitaemia recrudescence, it was observed that flow cytometry was a more sensitive methodology. The nine hydroxyethylamine derivatives were obtained by inserting one of the following radical in the para position: H, 4Cl, 4-Br, 4-F, 4-CH3, 4-OCH3, 4-NO2, 4-NH2 and 3-Br. The antimalarial test showed that the compound that received the methyl group (4-CH3 inhibited 70% of parasite growth. Our results suggest that GFP-transfected P. berghei is a useful tool to study the recrudescence of novel antimalarial drugs through parasitaemia examination by flow cytometry. Furthermore, it was demonstrated that the insertion of a methyl group at the para position of the sulfonamide ring appears to be critical for the antimalarial activity of this class of compounds.

  20. 4(1H)-Quinolones with liver stage activity against Plasmodium berghei.

    Science.gov (United States)

    Lacrue, Alexis N; Sáenz, Fabián E; Cross, R Matthew; Udenze, Kenneth O; Monastyrskyi, Andrii; Stein, Steven; Mutka, Tina S; Manetsch, Roman; Kyle, Dennis E

    2013-01-01

    With the exception of primaquine, tafenoquine, and atovaquone, there are very few antimalarials that target liver stage parasites. In this study, a transgenic Plasmodium berghei parasite (1052Cl1; PbGFP-Luc(con)) that expresses luciferase was used to assess the anti-liver stage parasite activity of ICI 56,780, a 7-(2-phenoxyethoxy)-4(1H)-quinolone (PEQ), as well as two 3-phenyl-4(1H)-quinolones (P4Q), P4Q-146 and P4Q-158, by using bioluminescent imaging (BLI). Results showed that all of the compounds were active against liver stage parasites; however, ICI 56,780 and P4Q-158 were the most active, with low nanomolar activity in vitro and causal prophylactic activity in vivo. This potent activity makes these compounds ideal candidates for advancement as novel antimalarials.

  1. Anti-malarial effect of 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one and green tea extract on erythrocyte-stage Plasmodium berghei in mice

    Institute of Scientific and Technical Information of China (English)

    Phitsinee; Thipubon; Wachiraporn; Tipsuwan; Chairat; Uthaipibull; Sineenart; Santitherakul; Somdet; Srichiratanakool

    2015-01-01

    Objective: To examine the efficacy of 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one(CM1) iron chelator and green tea extract(GTE) as anti-malarial activity in Plasmodium berghei(P. berghei) infected mice.Methods: The CM1(0–100 mg/kg/day) and GTE(0–100 mg(-)-epigallocatechin 3-gallate equivalent/kg/day) were orally administered to P. berghei infected mice for consecutive 4 days. Parasitized red blood cells(PRBC) were enumerated by using Giemsa staining microscopic method.Results: CM1 lowered percentage of PRBC in dose-dependent manner with an ED50 value of 56.91 mg/kg, when compared with pyrimethamine(PYR)(ED50= 0.76 mg/kg).GTE treatment did not show any inhibition of the malaria parasite growth. In combined treatment, CM1 along with 0.6 mg/kg PYR significantly inhibited the growth of P. berghei in mice while GTE did not enhance the PYR anti-malarial activity.Conclusions: CM1 would be effective per se and synergize with PYR in inhibiting growth of murine malaria parasites, possibly by limiting iron supply from plasma transferrin and host PRBC cytoplasm, and chelating catalytic iron cstitutive in parasites’ mitochondrial cytochromes and cytoplasmic ribonucleotide reductase. CM1 would be a promising adjuvant to enhance PYR anti-malarial activity and minimize the drug resistance.

  2. Anti-malarial effect of 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one and green tea extract on erythrocyte-stage Plasmodium berghei in mice

    Institute of Scientific and Technical Information of China (English)

    Phitsinee Thipubon; Wachiraporn Tipsuwan; Chairat Uthaipibull; Sineenart Santitherakul; Somdet Srichiratanakool

    2015-01-01

    Objective:To examine the efficacy of 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) iron chelator and green tea extract (GTE) as anti-malarial activity in Plasmodium berghei (P. berghei ) infected mice. Methods:The CM1 (0–100 mg/kg/day) and GTE (0–100 mg (-)-epigallocatechin 3-gallate equivalent/kg/day) were orally administered to P. berghei infected mice for consecutive 4 days. Parasitized red blood cells (PRBC) were enumerated by using Giemsa staining microscopic method. Results: CM1 lowered percentage of PRBC in dose-dependent manner with an ED50 value of 56.91 mg/kg, when compared with pyrimethamine (PYR) (ED50=0.76 mg/kg). GTE treatment did not show any inhibition of the malaria parasite growth. In combined treatment, CM1 along with 0.6 mg/kg PYR significantly inhibited the growth of P. berghei in mice while GTE did not enhance the PYR anti-malarial activity. Conclusions: CM1 would be effective per se and synergize with PYR in inhibiting growth of murine malaria parasites, possibly by limiting iron supply from plasma transferrin and host PRBC cytoplasm, and chelating catalytic iron constitutive in parasites’ mitochondrial cytochromes and cytoplasmic ribonucleotide reductase. CM1 would be a promising adjuvant to enhance PYR anti-malarial activity and minimize the drug resistance.

  3. AKTIVITAS ANTIMALARIA (IN VIVO KOMBINASI BUAH SIRIH (Piper betle L, DAUN MIYANA (Plectranthus scutellarioides (L. R. BR. MADU DAN KUNING TELUR PADA MEN CIT YANG DIINFEKSI Plasmodium berghei

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    Yun Astuti Nugroho

    2012-07-01

    Full Text Available Malaria is a major public health problem in the world and developing countries in particular, causing an estimated 1-2 million deaths per year, an annual incidence of 300-500 million clinical cases and more than 2 billion people were at risk of infection from it. But it is also becoming more difficult to treat malaria due to the increasing drug resistance. Therefore, the need for alternative drugs is acute. This study aims at investigating the in vivo antiplasmodial activity of Piper betle L., fruit (buah sirih, Plectranthus scutellarioides (L. R. BR., (daun miyana, honey and egg yolk combination. Methods: A rodent malaria parasite, Plasmodium berghei, was inoculated into Swiss albino mice. The mice were infected with Ixl05 parasites intraperitoneally. The Piper betle L., fruit (buah sirih, Plectranthus scutellarioides (L. R. BR., (daun miyana, honey and egg yolk combination were combined and administered by an intra gastric tube daily for seven days starting from the day of parasite inoculation. The control groups received the same amount of solvent (vehicle used to suspend each dose of the herbal drug. Chloroquine was used as a standard drug, administered through the same route. Results: Combination of Piper betle L., fruit (buah sirih, Plectranthus scutellarioides (L. R. BR., (daun miyana, honey and egg yolk were observed to inhibit Plasomodium berghei parasitaemia in the Swiss albino mice 100 % on the sixth day. Conclusion: The study could partly confirm the claim in East Sulawesi traditional medicine that the Piper betle L., fruit (buah sirih, Plectranthus scutellarioides (L. R. BR., (daun miyana, honey and egg yolk combination has therapeutic values in human malaria. There was, thus, the need to initiate further in-depth investigation by using different experimental models.

  4. AKTIVITAS ANTIMALARIA (IN VIVO KOMBINASI BUAH SIRIH (Piper betle L, DAUN MIYANA (Plectranthus scutellarioides (L. R. BR. MADU DAN KUNING TELUR PADA MEN CIT YANG DIINFEKSI Plasmodium berghei

    Directory of Open Access Journals (Sweden)

    Yun Astuti Nugroho

    2012-07-01

    Full Text Available Malaria is a major public health problem in the world and developing countries in particular, causing an estimated 1-2 million deaths per year, an annual incidence of 300-500 million clinical cases and more than 2 billion people were at risk of infection from it. But it is also becoming more difficult to treat malaria due to the increasing drug resistance. Therefore, the need for alternative drugs is acute. This study aims at investigating the in vivo antiplasmodial activity of Piper betle L., fruit (buah sirih, Plectranthus scutellarioides (L. R. BR., (daun miyana, honey and egg yolk combination. Methods: A rodent malaria parasite, Plasmodium berghei, was inoculated into Swiss albino mice. The mice were infected with Ixl05 parasites intraperitoneally. The Piper betle L., fruit (buah sirih, Plectranthus scutellarioides (L. R. BR., (daun miyana, honey and egg yolk combination were combined and administered by an intra gastric tube daily for seven days starting from the day of parasite inoculation. The control groups received the same amount of solvent (vehicle used to suspend each dose of the herbal drug. Chloroquine was used as a standard drug, administered through the same route. Results: Combination of Piper betle L., fruit (buah sirih, Plectranthus scutellarioides (L. R. BR., (daun miyana, honey and egg yolk were observed to inhibit Plasomodium berghei parasitaemia in the Swiss albino mice 100 % on the sixth day. Conclusion: The study could partly confirm the claim in East Sulawesi traditional medicine that the Piper betle L., fruit (buah sirih, Plectranthus scutellarioides (L. R. BR., (daun miyana, honey and egg yolk combination has therapeutic values in human malaria. There was, thus, the need to initiate further in-depth investigation by using different experimental models.

  5. Localization of MRNA storage complexes in Plasmodium berghei throughout the life cycle

    OpenAIRE

    Pereira, Marcelo Luís Monteiro

    2011-01-01

    Tese de mestrado. Biologia (Microbiologia Aplicada). Universidade de Lisboa, Faculdade de Ciências, 2011 Plasmodium is the causative agent of malaria, a disease that caused 781 thousands deaths during the year of 2009. The apicomplexan responsible for this disease have shown to be very well adapted to both mosquito and Vertebrate hosts, regulating its gene expression often in a posttranscriptional manner. Recently the protein HoMu and the translation initiation factor eIF4E (4E) were found...

  6. Epidemiology of Plasmodium vivax Malaria in Peru.

    Science.gov (United States)

    Rosas-Aguirre, Angel; Gamboa, Dionicia; Manrique, Paulo; Conn, Jan E; Moreno, Marta; Lescano, Andres G; Sanchez, Juan F; Rodriguez, Hugo; Silva, Hermann; Llanos-Cuentas, Alejandro; Vinetz, Joseph M

    2016-12-28

    Malaria in Peru, dominated by Plasmodium vivax, remains a public health problem. The 1990s saw newly epidemic malaria emerge, primarily in the Loreto Department in the Amazon region, including areas near to Iquitos, the capital city, but sporadic malaria transmission also occurred in the 1990s-2000s in both north-coastal Peru and the gold mining regions of southeastern Peru. Although a Global Fund-supported intervention (PAMAFRO, 2005-2010) was temporally associated with a decrease of malaria transmission, from 2012 to the present, both P. vivax and Plasmodium falciparum malaria cases have rapidly increased. The Peruvian Ministry of Health continues to provide artemesinin-based combination therapy for microscopy-confirmed cases of P. falciparum and chloroquine-primaquine for P. vivax Malaria transmission continues in remote areas nonetheless, where the mobility of humans and parasites facilitates continued reintroduction outside of ongoing surveillance activities, which is critical to address for future malaria control and elimination efforts. Ongoing P. vivax research gaps in Peru include the following: identification of asymptomatic parasitemics, quantification of the contribution of patent and subpatent parasitemics to mosquito transmission, diagnosis of nonparasitemic hypnozoite carriers, and implementation of surveillance for potential emergence of chloroquine- and 8-aminoquinoline-resistant P. vivax Clinical trials of tafenoquine in Peru have been promising, and glucose-6-phosphate dehydrogenase deficiency in the region has not been observed to be a limitation to its use. Larger-scale challenges for P. vivax (and malaria in general) in Peru include logistical difficulties in accessing remote riverine populations, consequences of government policy and poverty trends, and obtaining international funding for malaria control and elimination.

  7. Epidemiology of Plasmodium vivax Malaria in Peru

    Science.gov (United States)

    Rosas-Aguirre, Angel; Gamboa, Dionicia; Manrique, Paulo; Conn, Jan E.; Moreno, Marta; Lescano, Andres G.; Sanchez, Juan F.; Rodriguez, Hugo; Silva, Hermann; Llanos-Cuentas, Alejandro; Vinetz, Joseph M.

    2016-01-01

    Malaria in Peru, dominated by Plasmodium vivax, remains a public health problem. The 1990s saw newly epidemic malaria emerge, primarily in the Loreto Department in the Amazon region, including areas near to Iquitos, the capital city, but sporadic malaria transmission also occurred in the 1990s–2000s in both north-coastal Peru and the gold mining regions of southeastern Peru. Although a Global Fund-supported intervention (PAMAFRO, 2005–2010) was temporally associated with a decrease of malaria transmission, from 2012 to the present, both P. vivax and Plasmodium falciparum malaria cases have rapidly increased. The Peruvian Ministry of Health continues to provide artemesinin-based combination therapy for microscopy-confirmed cases of P. falciparum and chloroquine–primaquine for P. vivax. Malaria transmission continues in remote areas nonetheless, where the mobility of humans and parasites facilitates continued reintroduction outside of ongoing surveillance activities, which is critical to address for future malaria control and elimination efforts. Ongoing P. vivax research gaps in Peru include the following: identification of asymptomatic parasitemics, quantification of the contribution of patent and subpatent parasitemics to mosquito transmission, diagnosis of nonparasitemic hypnozoite carriers, and implementation of surveillance for potential emergence of chloroquine- and 8-aminoquinoline-resistant P. vivax. Clinical trials of tafenoquine in Peru have been promising, and glucose-6-phosphate dehydrogenase deficiency in the region has not been observed to be a limitation to its use. Larger-scale challenges for P. vivax (and malaria in general) in Peru include logistical difficulties in accessing remote riverine populations, consequences of government policy and poverty trends, and obtaining international funding for malaria control and elimination. PMID:27799639

  8. The protective effect of Moringa oleifera leaf extract on liver damage in mice infected with Plasmodium berghei ANKA

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    Kittiyaporn Dondee

    2016-09-01

    Full Text Available Objective: To investigate the protective effect of Moringa oleifera leaf extract on liver damage in mice infected with Plasmodium berghei ANKA (P. berghei Methods: For extraction of Moringa oleifera (M. oleifera leaves, microwave with hot water method was used and acute toxicity study was then be done. Standard Peters’ test was carried out to test the efficacy of M. oleifera extract in vivo. The ICR mice were inoculated with 1 × 107 red blood cells infected with P. berghei strain by intraperitoneal injection. They were subsequently given with 100, 500 and 1000 mg/kg of this extract by intragastric route once a day for 4 consecutive days. Parasitemia was estimated using microscopy and levels of aspartate aminotransferase, alanine aminotransferase and albumin were also measured. Results: The M. oleifera leaf extract showed the protective activity on liver damage in mice infected with P. berghei in a dose-dependent fashion. It can be indicated by normal levels of aspartate aminotransferase, alanine aminotransferase and albumin in mice treated with extract. The 1000 mg/kg of extract was observed to present the highest activity. Interestingly, the dosedependent antimalarial activity was also found in the mice treated with extract. Conclusions: The M. oleifera leaf extract presented protective effect on liver damage in mice infected with P. berghei.

  9. Plasmodium vivax malaria during pregnancy, Bolivia.

    Science.gov (United States)

    Brutus, Laurent; Santalla, José; Schneider, Dominique; Avila, Juan Carlos; Deloron, Philippe

    2013-10-01

    Plasmodium vivax is a major cause of illness in areas with low transmission of malaria in Latin America, Asia, and the Horn of Africa. However, pregnancy-associated malaria remains poorly characterized in such areas. Using a hospital-based survey of women giving birth and an antenatal survey, we assessed the prevalence rates of Plasmodium spp. infections in pregnant women in Bolivia, and evaluated the consequences of malaria during pregnancy on the health of mothers and newborns. P. vivax infection was detected in 7.9% of pregnant women attending antenatal visits, and placental infection occurred in 2.8% of deliveries; these rates did not vary with parity. Forty-two percent of all P. vivax malaria episodes were symptomatic. P. vivax-infected pregnant women were frequently anemic (6.5%) and delivered babies of reduced birthweight. P. vivax infections during pregnancy are clearly associated with serious adverse outcomes and should be considered in prevention strategies of pregnancy-associated malaria.

  10. Guillain-Barré syndrome in Plasmodium falciparum malaria.

    OpenAIRE

    Wijesundere, A.

    1992-01-01

    A patient with Plasmodium falciparum malaria developed peripheral neuropathy. Clinical, cerebro-spinal fluid examination and nerve conduction studies confirmed Guillain-Barré syndrome, not previously reported in P. falciparum malaria.

  11. Plasmodium berghei Δp52&p36 parasites develop independent of a parasitophorous vacuole membrane in Huh-7 liver cells.

    Science.gov (United States)

    Ploemen, Ivo H J; Croes, Huib J; van Gemert, Geert-Jan J; Wijers-Rouw, Mietske; Hermsen, Cornelus C; Sauerwein, Robert W

    2012-01-01

    The proteins P52 and P36 are expressed in the sporozoite stage of the murine malaria parasite Plasmodium berghei. Δp52&p36 sporozoites lacking expression of both proteins are severely compromised in their capability to develop into liver stage parasites and abort development soon after invasion; presumably due to the absence of a parasitophorous vacuole membrane (PVM). However, a small proportion of P. berghei Δp52&p36 parasites is capable to fully mature in hepatocytes causing breakthrough blood stage infections. We have studied the maturation of replicating Δp52&p36 parasites in cultured Huh-7 hepatocytes. Approximately 50% of Δp52&p36 parasites developed inside the nucleus of the hepatocyte but did not complete maturation and failed to produce merosomes. In contrast cytosolic Δp52&p36 parasites were able to fully mature and produced infectious merozoites. These Δp52&p36 parasites developed into mature schizonts in the absence of an apparent parasitophorous vacuole membrane as shown by immunofluorescence and electron microscopy. Merozoites derived from these maturing Δp52&p36 liver stages were infectious for C57BL/6 mice.

  12. Antimalarial Properties of Aqueous Crude Extracts of Gynostemma pentaphyllum and Moringa oleifera Leaves in Combination with Artesunate in Plasmodium berghei-Infected Mice.

    Science.gov (United States)

    Somsak, Voravuth; Borkaew, Preeyanuch; Klubsri, Chokdee; Dondee, Kittiyaporn; Bootprom, Panatda; Saiphet, Butsarat

    2016-01-01

    Due to the emergence and spread of malaria parasite with resistance to antimalarial drugs, discovery and development of new, safe, and affordable antimalarial are urgently needed. In this respect, medicinal plant extracts are targets to optimize antimalarial actions and restore efficacy of standard antimalarial drugs. The present study was aimed at determining the antimalarial activities of Gynostemma pentaphyllum and Moringa oleifera leaf extracts in combination with artesunate against Plasmodium berghei-infected mice. P. berghei ANKA maintained by serial passage in ICR mice were used based on intraperitoneal injection of 1 × 10(7) parasitized erythrocytes and subsequent development of parasitemia. These infected mice were used to investigate the antimalarial activity of artesunate (6 mg/kg) in combination with 500, 1,000, and 2,000 mg/kg of G. pentaphyllum and M. oleifera leaf extracts using 4-day suppressive test. It was found that these extracts showed significant (P pentaphyllum leaf extract and 35, 40, and 50% for M. oleifera leaf extract. Additionally, artesunate combined with these extracts presented higher antimalarial activity, compared to extract treated alone with percentage of suppression of 78, 91, and 96% for G. pentaphyllum leaf extract and 73, 82, and 91% for M. oleifera leaf extract. The results indicated that combination treatment of G. pentaphyllum or M. oleifera leaf extracts with artesunate was able to increase the antimalarial activity by using low dose of artesunate. Hence, these results justified the combination of these extracts and artesunate in antimalarial herbal remedies.

  13. Evaluation of the Effectiveness of Ethanolic Extract of Solanum Surattense against Plasmodium Berghei in Comparison with Chloroquine in Sourian Mice Using in Vivo Tests

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    Garedaghi Yagoob

    2014-07-01

    Full Text Available Objective: Owing to the importance of employing native and traditional medicinal plants with good efficacy against malaria parasites, an ethanolic extract of Solanum surattense was tested on Plasmodium berghei in sourian mice. Moreover, the results were compared with that of the effect of chloroquine on the same parasite. Materials and Methods: In this study, 80 sourian mice were divided into 8 groups, each consisting of 10 animals. The first 7 groups were infected with P. berghei and the last group was used as control. The first 7 groups were given chloroquine, solanum surattense at four different concentrations (20, 100, 300, and 450 mg/kg, and placebo, respectively, and the seventh group did not receive any treatment. The evaluation was done by Rane test. In each group, the level of parasitaemia was determined on days 4 and 7, and compared with values from day 0 (just before treatment in order to record the decline in parasitaemia in treated groups. Results were analyzed using SPSS software and one-way analysis of variance (ANOVA. Results: The results indicated that although all four concentrations of Solanum surattense extract significantly reduced parasitaemia in the infected subjects, the 450 mg/kg solution showed optimal effectiveness on the parasites in comparison with other concentrations and the no-treatment option. Conclusion: We conclude that although the ethanolic extract of Solanum surattense is not as effective as chloroquine in reducing parasitaemia, it can nonetheless cause a significant decrease when compared to control and placebo groups.

  14. Plasmodium berghei Δp52&p36 parasites develop independent of a parasitophorous vacuole membrane in Huh-7 liver cells.

    Directory of Open Access Journals (Sweden)

    Ivo H J Ploemen

    Full Text Available The proteins P52 and P36 are expressed in the sporozoite stage of the murine malaria parasite Plasmodium berghei. Δp52&p36 sporozoites lacking expression of both proteins are severely compromised in their capability to develop into liver stage parasites and abort development soon after invasion; presumably due to the absence of a parasitophorous vacuole membrane (PVM. However, a small proportion of P. berghei Δp52&p36 parasites is capable to fully mature in hepatocytes causing breakthrough blood stage infections. We have studied the maturation of replicating Δp52&p36 parasites in cultured Huh-7 hepatocytes. Approximately 50% of Δp52&p36 parasites developed inside the nucleus of the hepatocyte but did not complete maturation and failed to produce merosomes. In contrast cytosolic Δp52&p36 parasites were able to fully mature and produced infectious merozoites. These Δp52&p36 parasites developed into mature schizonts in the absence of an apparent parasitophorous vacuole membrane as shown by immunofluorescence and electron microscopy. Merozoites derived from these maturing Δp52&p36 liver stages were infectious for C57BL/6 mice.

  15. Antimalarial efficacy of Albizia lebbeck (Leguminosae against Plasmodium falciparum in vitro & P. berghei in vivo

    Directory of Open Access Journals (Sweden)

    Shagun Kalia

    2015-01-01

    Full Text Available Background & objectives: Albizia lebbeck Benth. (Leguminosae has long been used in Indian traditional medicine. The current study was designed to test antimalarial activity of ethanolic bark extract of A. lebbeck (EBEAL. Methods: EBEAL was prepared by soxhlet extraction and subjected to phytochemical analysis. The extract was evaluated for its in vitro antimalarial activity against Plasmodium falciparum chloroquine (CQ sensitive (MRC2 and CQ resistant (RKL9 strains. Cytotoxicity (CC 50 of extract against HeLa cells was evaluated. Median lethal dose (LD 50 was determined to assess safety of EBEAL in BALB/c mice. Schizonticidal (100-1000 mg/kg and preventive (100-750 mg/kg activities of EBEAL were evaluated against P. berghei. Curative activity (100-750 mg/kg of extract was also evaluated. Results: Phytochemical screening revealed presence of alkaloids, flavonoids, phenols, saponins, terpenes and phytosterols. The extract exhibited IC 50 of 8.2 µg/ml (MRC2 and 5.1 µg/ml (RKL9. CC 50 of extract on HeLa cell line was calculated to be >1000 µg/ml. EBEAL showed selectivity indices (SI of >121.9 and >196.07 against MRC2 and RKL9 strains of P. falciparum, respectively. LD 50 of EBEAL was observed to be >5 g/kg. Dose-dependent chemosuppression was observed with significant ( p100 mg/kg. Significant (P<0.001 curative and repository activities were exhibited by 750 mg/kg concentration of extract on D7. Interpretation & conclusions: The present investigation reports antiplasmodial efficacy of EBEAL in vitro against P. falciparum as evident by high SI values. ED 50 of <100 mg/kg against P. berghei categorizes EBEAL as active antimalarial. Further studies need to be done to exploit its antiplasmodial activity further.

  16. Efeito de Momordica charantia I. Em camundongos infectados por Plasmodium berghei

    Directory of Open Access Journals (Sweden)

    Helene Mariko Ueno

    1996-10-01

    Full Text Available A Organização Mundial de Saúde (OMS citou a malãria como um dos principais problemas de saúde no Brasil e no terceiro mundo, onde 80% da população recorre à medicina tradicional (popular para sanar vários problemas de assistência médica primária. No que se refere à malária, seu tratamento e controle têm sido dificultados devido às cepas resistentes às drogas comumente utilizadas. Isso torna urgente a busca de novas drogas antimaláncas. Sabe-se que a população utiliza-se de diferentes plantas para o tratamento e cura de vários males, inclusive a malãria. Neste trabalho nos propusemos reavaliar o efeito de Momordica charantia L. (Cucurbitaceae sobre camundongos infectados por Plasmodium berghei. A planta foi testada sob a forma de extratos aquoso e etanólico, na dose de lOOOmg por kg cle peso coipóreo do camundongo, ministrado por via oral, por cinco dias consecutivos da infecção (2º ao 6º. O efeito foi avaliado em função da parasitemia e da sobrevida dos animais. Embora a população indique e utilize essa planta na malária humana, nos ensaios deste trabalho, nas condições do experimento, os extratos de M. charantia não apresentaram atividade satisfatória contra o P. berghei.

  17. 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 ...

  18. Effect of N-Acetyl Cysteine administration to the degree of parasitemia and plasma interleukin-12 level of mice infected with plasmodium berghei and treated with artemisinin

    Directory of Open Access Journals (Sweden)

    Loeki E. Fitri

    2009-03-01

    Full Text Available Introduction Protection against malaria requires a cell-mediated immune response which is initiated by releasing interleukin-12 (IL-12 from antigen presenting cells (APC. N-Acetyl Cysteine (NAC is a precursor of glutathione, while glutathione itself increases IL-12 production. Treatment with NAC combined with artemisinin is supposed to increase cellular immunity of mice during Plasmodium berghei infection. The aim of this study was to measure the effects of NAC administration on the degree of parasitemia and plasma IL-12 level in mice infected with P. berghei and treated with artemisinin.Methods The research was done using post-test-control-only design using 5 groups: group A (negative control group, group B (positive control group, or mice infected with P.berghei without therapy, group C ( mice infected by P.berghei and received artemisinin 0.04 mg/g BW for 7 days, group D (mice infected with P.berghei and received artemisinin in combination with NAC 1 mg/g BW for 7 days and group E (mice infected wirth P.berghei and received artemisinin in  combination with NAC 1 mg/g BW for 3 days and tapered into ½ mg/g BW for 4 days. Parasitemia was followed up every two days. Approximately six days post infection or when the degree of parasitemia reached ± 10% therapy was begun. On the 3rd, 5th, and 7th days post therapy, mice from each group were terminated and assayed for plasma IL-12 level (ELISA, Bender Medsystems GmbH, Vienna, cat. BMS6004.Results All mice treated with artemisinin mono-therapy and combined therapy had significantly decreased parasitemia (P=0.000. There was no significant difference (P>0.05 in decreasing parasitemia among treatment groups. The plasma IL-12 level increased significantly in both groups that received the combination of artemisinin and NAC constant dose and tapering dose compared with the group that received artemisinin mono-therapy (p < 0,05. Plasma IL-12p70 level in the combination of artemisinin and NAC tapering dose

  19. Identification of Protective B-Cell Epitopes within the Novel Malaria Vaccine Candidate Plasmodium falciparum Schizont Egress Antigen 1.

    Science.gov (United States)

    Nixon, Christina E; Park, Sangshin; Pond-Tor, Sunthorn; Raj, Dipak; Lambert, Lynn E; Orr-Gonzalez, Sachy; Barnafo, Emma K; Rausch, Kelly M; Friedman, Jennifer F; Fried, Michal; Duffy, Patrick E; Kurtis, Jonathan D

    2017-07-01

    Naturally acquired antibodies to Plasmodium falciparum schizont egress antigen 1 (PfSEA-1A) are associated with protection against severe malaria in children. Vaccination of mice with SEA-1A from Plasmodium berghei (PbSEA-1A) decreases parasitemia and prolongs survival following P. berghei ANKA challenge. To enhance the immunogenicity of PfSEA-1A, we identified five linear B-cell epitopes using peptide microarrays probed with antisera from nonhuman primates vaccinated with recombinant PfSEA-1A (rPfSEA-1A). We evaluated the relationship between epitope-specific antibody levels and protection from parasitemia in a longitudinal treatment-reinfection cohort in western Kenya. Antibodies to three epitopes were associated with 16 to 17% decreased parasitemia over an 18-week high transmission season. We are currently designing immunogens to enhance antibody responses to these three epitopes. Copyright © 2017 American Society for Microbiology.

  20. Development of vaccines for Plasmodium vivax malaria.

    Science.gov (United States)

    Mueller, Ivo; Shakri, Ahmad Rushdi; Chitnis, Chetan E

    2015-12-22

    Plasmodium vivax continues to cause significant morbidity outside Africa with more than 50% of malaria cases in many parts of South and South-east Asia, Pacific islands, Central and South America being attributed to P. vivax infections. The unique biology of P. vivax, including its ability to form latent hypnozoites that emerge months to years later to cause blood stage infections, early appearance of gametocytes before clinical symptoms are apparent and a shorter development cycle in the vector makes elimination of P. vivax using standard control tools difficult. The availability of an effective vaccine that provides protection and prevents transmission would be a valuable tool in efforts to eliminate P. vivax. Here, we review the latest developments related to P. vivax malaria vaccines and discuss the challenges as well as directions toward the goal of developing highly efficacious vaccines against P. vivax malaria.

  1. Antiplasmodial activity of eco-friendly synthesized palladium nanoparticles using Eclipta prostrata extract against Plasmodium berghei in Swiss albino mice.

    Science.gov (United States)

    Rajakumar, Govindasamy; Rahuman, Abdul Abdul; Chung, Ill-Min; Kirthi, Arivarasan Vishnu; Marimuthu, Sampath; Anbarasan, Karunanithi

    2015-04-01

    Malaria is an infectious disease caused by the Plasmodium parasite that continues to be a health issue for humans. It is one of the most common pathogenic factors of morbidity and mortality. Palladium nanoparticles (Pd NPs) have been used as target antimicrobial compounds, as a catalyst to manufacture pharmaceuticals, degrade harmful environmental pollutants, and as sensors for the detection of various analyses. The aim of this study was to investigate the antiplasmodial activity of synthesized Pd NPs by using leaf aqueous extract of Eclipta prostrata against Plasmodium berghei in Swiss albino mice. The synthesized Pd NPs were characterized by X-ray diffraction (XRD), Fourier transform infrared (FTIR), Scanning electron microscopy (SEM) with Energy dispersive X-ray spectroscopy (EDX), and High-resolution transmission electron microscope (HRTEM) with the Selected area (electron) diffraction (SAED). The XRD peaks appeared at 35.61°, 44.27°, 56.40°, and 74.51°, which correspond to (111), (200), (220), and (311) planes for palladium, respectively. The FTIR spectra that were carried out to identify the potential biomolecule of synthesized Pd NPs showed the peaks at 3361, 1540, 1399, 1257, 1049, and 659 in the region of 4000-500 cm(-1). The SEM images showed aggregation of NPs with an average size of 63 ± 1.4. The HRTEM images of the precipitated solid phase obtained after termination of the reaction of E. prostrata aqueous leaf extract were in the range from 18 to 64 nm with an average size of 27 ± 1.3 nm. The in vivo antiplasmodial assay was carried out as per Peters' 4-day suppressive test, and the synthesized Pd NP-treated mice group showed reduction of parasitemia by 78.13% with an inhibitory concentration (IC)50 value of 16.44 mg/kg/body weight. The growth inhibition of E. prostrata aqueous leaf extract, palladium acetate, and synthesized Pd NPs showed the IC20, IC50, and IC90 values of 1.90, 10.29, and 64.11; 4.49, 9.84, and 23.04; and 4.34, 8

  2. Dendritic cells treated with crude Plasmodium berghei extracts acquire immune-modulatory properties and suppress the development of autoimmune neuroinflammation.

    Science.gov (United States)

    Thomé, Rodolfo; Issayama, Luidy K; Alves da Costa, Thiago; Gangi, Rosária D; Ferreira, Isadora T; Rapôso, Catarina; Lopes, Stefanie C P; da Cruz Höfling, Maria Alice; Costa, Fábio T M; Verinaud, Liana

    2014-10-01

    Dendritic cells (DCs) are professional antigen-presenting cells specifically targeted during Plasmodium infection. Upon infection, DCs show impaired antigen presentation and T-cell activation abilities. In this study, we aimed to evaluate whether cellular extracts obtained from Plasmodium berghei-infected erythrocytes (PbX) modulate DCs phenotypically and functionally and the potential therapeutic usage of PbX-modulated DCs in the control of experimental autoimmune encephalomyelitis (EAE, the mouse model for human multiple sclerosis). We found that PbX-treated DCs have impaired maturation and stimulated the generation of regulatory T cells when cultured with naive T lymphocytes in vitro. When adoptively transferred to C57BL/6 mice the EAE severity was reduced. Disease amelioration correlated with a diminished infiltration of cytokine-producing T cells in the central nervous system as well as the suppression of encephalitogenic T cells. Our study shows that extracts obtained from P. berghei-infected erythrocytes modulate DCs towards an immunosuppressive phenotype. In addition, the adoptive transfer of PbX-modulated DCs was able to ameliorate EAE development through the suppression of specific cellular immune responses towards neuro-antigens. To our knowledge, this is the first study to present evidence that DCs treated with P. berghei extracts are able to control autoimmune neuroinflammation.

  3. Attempted isolation of the gene encoding the 21 Kd Plasmodium berghei ookinete transmission blocking antigen from Plasmodium yoelli and Plasmodium vivax

    Directory of Open Access Journals (Sweden)

    G. C. Barker

    1994-01-01

    Full Text Available The 21kD ookinete antigen of Plasmodium berghei (Pbs 21 has been shown to elicit an effective and long lasting transmission blocking immune response in mice. Having cloned and sequenced this antigen (Paton et al. 1993 the sequence was compared to the genes of the same family previously identified in P. falciparum, P. gallinaceum (Kaslow et al. 1989 and P. reichenowi (Lal et al. 1990. Four conserved areas were identified in this comparison, to which degenerate oligonucleotides were designed. PCR amplification and screening of genomic libraries was then carried out using these oligonucleotides. The P. yoelii gene was successfully cloned and a number of novel P. vivax genes identified but the P. vivax homologue of Pbs21 remains elusive.

  4. Plasmodium knowlesi malaria in Vietnam: some clarifications

    Directory of Open Access Journals (Sweden)

    Hung Le

    2010-01-01

    Full Text Available Abstract A recently published comment on a report of Plasmodium knowlesi infections in Vietnam states that this may not accurately represent the situation in the study area because the PCR primers used may cross-hybridize with Plasmodium vivax. Nevertheless, P. knowlesi infections have been confirmed by sequencing. In addition, a neighbour-joining tree based on the 18S S-Type SSUrRNA gene shows that the Vietnamese samples clearly cluster with the P. knowlesi isolates identified in Malaysia and are distinct from the corresponding P. vivax sequences. All samples came from asymptomatic individuals who did not consult for fever during the months preceding or following the survey, indicating that asymptomatic P. knowlesi infections occur in this population, although this does not exclude the occurrence of symptomatic cases. Large-scale studies to determine the extent and the epidemiology of P. knowlesi malaria in Vietnam are further needed.

  5. Primate malarias: Diversity, distribution and insights for zoonotic Plasmodium

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    Christina Faust

    2015-12-01

    Full Text Available Protozoans within the genus Plasmodium are well-known as the causative agents of malaria in humans. Numerous Plasmodium species parasites also infect a wide range of non-human primate hosts in tropical and sub-tropical regions worldwide. Studying this diversity can provide critical insight into our understanding of human malarias, as several human malaria species are a result of host switches from non-human primates. Current spillover of a monkey malaria, Plasmodium knowlesi, in Southeast Asia highlights the permeability of species barriers in Plasmodium. Also recently, surveys of apes in Africa uncovered a previously undescribed diversity of Plasmodium in chimpanzees and gorillas. Therefore, we carried out a meta-analysis to quantify the global distribution, host range, and diversity of known non-human primate malaria species. We used published records of Plasmodium parasites found in non-human primates to estimate the total diversity of non-human primate malarias globally. We estimate that at least three undescribed primate malaria species exist in sampled primates, and many more likely exist in unstudied species. The diversity of malaria parasites is especially uncertain in regions of low sampling such as Madagascar, and taxonomic groups such as African Old World Monkeys and gibbons. Presence–absence data of malaria across primates enables us to highlight the close association of forested regions and non-human primate malarias. This distribution potentially reflects a long coevolution of primates, forest-adapted mosquitoes, and malaria parasites. The diversity and distribution of primate malaria are an essential prerequisite to understanding the mechanisms and circumstances that allow Plasmodium to jump species barriers, both in the evolution of malaria parasites and current cases of spillover into humans.

  6. Plasmodium falciparum transcriptome analysis reveals pregnancy malaria associated gene expression

    DEFF Research Database (Denmark)

    Tuikue Ndam, Nicaise; Bischoff, Emmanuel; Proux, Caroline

    2008-01-01

    BACKGROUND: Pregnancy-associated malaria (PAM) causing maternal anemia and low birth weight is among the multiple manifestations of Plasmodium falciparum malaria. Infected erythrocytes (iEs) can acquire various adhesive properties that mediate the clinical severity of malaria. Recent advances...

  7. Latent Infections with Plasmodium ovale Malaria

    Science.gov (United States)

    Miller, Max J.; Marcus, David M.; Cameron, Douglas G.

    1965-01-01

    Two cases of Plasmodium ovale malaria acquired in West Africa appeared as primary delayed attacks after one year's continuous residence in Canada. Both patients took full prophylactic doses of chloroquine before, during, and for several weeks after exposure. The inadequacy of the 4-aminoquinolines for protection against latent benign tertian malaria is noted, and the use of primaquine is recommended. Paroxysms occurred in the evening and were accompanied by severe muscle pain, features considered typical of ovale malaria. One patient showed electrocardiographic changes and clinical signs of cardiac malfunction; these disappeared following specific treatment for malaria. In this age of accelerated travel and international movements of people it is important that physicians in temperate regions be aware of the exotic infections of the tropics, as well as of the need for protective measures for travellers to areas where these diseases are endemic. ImagesFig. 1aFig. 1b,1cFig. 3 a-dFig. 3 e-h PMID:14296004

  8. Pharmacodynamic evaluation for antiplasmodial activity of Holarrhena antidysentrica (Kutaja) and Azadirachta indica (Neemb) in Plasmodium berghei infected mice model

    Institute of Scientific and Technical Information of China (English)

    Jadhav Priyanka; Lal Hingorani; Kshirsagar Nilima

    2013-01-01

    Objective: To investigate in-vivo anti-plasmodial activity of aqueous extracts of plants selected based on the symptomology mentioned in Ayurveda. Methods: The aqueous extracts of Holarrhena antidysentrica (H. antidysentrica) (Kutaja) and Azadirachta indica (A. indica) (Neemb) for their antiplasmodial potential in Plasmodium berghei (P. berghei) infected mice was assessed using Peters four day suppressive test. Both the extracts were administered at 2 dose levels, full dose (1 000 mg/d) and minimized dose (200 mg/d). 106 P. berghei infected RBCs were injected on day ’0’ and treated from day ’0’ till day ’3’ post-infection. Tail blood smears were collected, giemsa stained and analyzed. The mice were observed for survival and parasitemia was assessed till 50% of mice in control survived. Results: It was observed that the percentage of parasitemia increased gradually in all the groups, with maximum in control group (Day 3-35, Day 9-46.98) and minimum in Chloroquine arm (Day 3-14.06, Day 9-19.92). The percentage of parasitemia was compared using Mann-Whitney U test depicting that all test groups exhibited reduction in parasitemia as compared to control (P-value<0.002 for all groups). These groups showed similar percentage of survival as Chloroquine. Conclusions: The present investigation demonstrated the anti-plasmodial effects of H. antidysentrica and A. indica, which are two most commonly used medicinal plants in Ayurved for treatment of fever.

  9. Effect of Crocus sativus Stigma (saffron alone or in combination with chloroquine on chloroquine sensitive strain of Plasmodium berghei in mice

    Directory of Open Access Journals (Sweden)

    Pestechian Nader

    2015-10-01

    Full Text Available Introduction: In malaria treatment protocols, treatment failure or drug resistance of synthesized drugs like alkaloids related to quinine, and aminoquinolines are the main problems now. Therefore, discovering efficient drugs or combination therapy of blood schizonticidal drugs with different mechanisms or different targets in the parasite is a crucial effort to solve this problem. In this study, the effectiveness of Crocus sativus Stigma (saffron individually and in combination with chloroquine, was considered against chloroquine–sensitive strain of Plasmodium berghei.Methods: At the first stage, using 4 day suppressive Peter’s test in mice, ED50 and survival times of saffron methanol extract, and its aqueous and ethyl acetate fractions and chloroquine on P. berghei were calculated. Then, based on the toxicity and survival time results, combination therapy was conducted with the best saffron fraction and chloroquine against the parasite.Results: The saffron extract, aqueous and ethyl acetate fractions resulted in suppression of parasitemia with ED50 values of 587.0 ± 78.7, 323.7 ± 37.2, and 508.7 ± 35.6 mg/kg, respectively. Combination of ethyl acetate fraction with chloroquine, potentiated the antimalarial property and the survived percent of the treated mice on days 7, 14, and 28 significantly more than chloroquine or ethyl acetate fraction alone.Conclusion: Saffron and its fractions individually can be effective in reducing the parasitemia in mice. The outcome of combination of ethyl acetate fraction with chloroquine on the mice showed synergistic effect on the chloroquine–sensitive strain of parasite.

  10. Antimalarial Properties of Aqueous Crude Extracts of Gynostemma pentaphyllum and Moringa oleifera Leaves in Combination with Artesunate in Plasmodium berghei-Infected Mice

    Science.gov (United States)

    Borkaew, Preeyanuch; Klubsri, Chokdee; Dondee, Kittiyaporn; Bootprom, Panatda; Saiphet, Butsarat

    2016-01-01

    Due to the emergence and spread of malaria parasite with resistance to antimalarial drugs, discovery and development of new, safe, and affordable antimalarial are urgently needed. In this respect, medicinal plant extracts are targets to optimize antimalarial actions and restore efficacy of standard antimalarial drugs. The present study was aimed at determining the antimalarial activities of Gynostemma pentaphyllum and Moringa oleifera leaf extracts in combination with artesunate against Plasmodium berghei-infected mice. P. berghei ANKA maintained by serial passage in ICR mice were used based on intraperitoneal injection of 1 × 107 parasitized erythrocytes and subsequent development of parasitemia. These infected mice were used to investigate the antimalarial activity of artesunate (6 mg/kg) in combination with 500, 1,000, and 2,000 mg/kg of G. pentaphyllum and M. oleifera leaf extracts using 4-day suppressive test. It was found that these extracts showed significant (P < 0.05) antimalarial activity in dose-dependent manner with percentage of suppression of 45, 50, and 55% for G. pentaphyllum leaf extract and 35, 40, and 50% for M. oleifera leaf extract. Additionally, artesunate combined with these extracts presented higher antimalarial activity, compared to extract treated alone with percentage of suppression of 78, 91, and 96% for G. pentaphyllum leaf extract and 73, 82, and 91% for M. oleifera leaf extract. The results indicated that combination treatment of G. pentaphyllum or M. oleifera leaf extracts with artesunate was able to increase the antimalarial activity by using low dose of artesunate. Hence, these results justified the combination of these extracts and artesunate in antimalarial herbal remedies. PMID:27872647

  11. Antimalarial Properties of Aqueous Crude Extracts of Gynostemma pentaphyllum and Moringa oleifera Leaves in Combination with Artesunate in Plasmodium berghei-Infected Mice

    Directory of Open Access Journals (Sweden)

    Voravuth Somsak

    2016-01-01

    Full Text Available Due to the emergence and spread of malaria parasite with resistance to antimalarial drugs, discovery and development of new, safe, and affordable antimalarial are urgently needed. In this respect, medicinal plant extracts are targets to optimize antimalarial actions and restore efficacy of standard antimalarial drugs. The present study was aimed at determining the antimalarial activities of Gynostemma pentaphyllum and Moringa oleifera leaf extracts in combination with artesunate against Plasmodium berghei-infected mice. P. berghei ANKA maintained by serial passage in ICR mice were used based on intraperitoneal injection of 1 × 107 parasitized erythrocytes and subsequent development of parasitemia. These infected mice were used to investigate the antimalarial activity of artesunate (6 mg/kg in combination with 500, 1,000, and 2,000 mg/kg of G. pentaphyllum and M. oleifera leaf extracts using 4-day suppressive test. It was found that these extracts showed significant (P<0.05 antimalarial activity in dose-dependent manner with percentage of suppression of 45, 50, and 55% for G. pentaphyllum leaf extract and 35, 40, and 50% for M. oleifera leaf extract. Additionally, artesunate combined with these extracts presented higher antimalarial activity, compared to extract treated alone with percentage of suppression of 78, 91, and 96% for G. pentaphyllum leaf extract and 73, 82, and 91% for M. oleifera leaf extract. The results indicated that combination treatment of G. pentaphyllum or M. oleifera leaf extracts with artesunate was able to increase the antimalarial activity by using low dose of artesunate. Hence, these results justified the combination of these extracts and artesunate in antimalarial herbal remedies.

  12. International population movements and regional Plasmodium falciparum malaria elimination strategies

    National Research Council Canada - National Science Library

    Andrew J. Tatem; David L. Smith; Susan Hanson

    2010-01-01

    ... to areas targeted for elimination. Here, census-based migration data were analyzed with network analysis tools, Plasmodium falciparum malaria transmission maps, and global population databases to map globally communities of countries...

  13. Heterologous Protection against Malaria after Immunization with Plasmodium falciparum Sporozoites

    NARCIS (Netherlands)

    Schats, R.; Bijker, E.M.; Gemert, G.J.A. van; Graumans, W.; Vegte-Bolmer, M. van de; Lieshout, L. van; Haks, M.C.; Hermsen, C.C.; Scholzen, A.; Visser, L.G.; Sauerwein, R.W.

    2015-01-01

    BACKGROUND: Sterile protection in >90% of volunteers against homologous Plasmodium falciparum infection has been achieved only using the controlled human malaria infection (CHMI) model. This efficient model involves whole parasite immunizations under chloroquine prophylaxis (CPS-immunization),

  14. Antiplasmodial effects of the aqueous ethanolic seed extract of Ziziphus mauritiana against Plasmodium berghei in Swiss albino mice

    Directory of Open Access Journals (Sweden)

    Tulika Mishra

    2014-08-01

    Full Text Available Ziziphus mauritiana is a fruit tree used traditionally since long back for wound healing, immunepotentiator, asthma, sedative, stomachic, styptic, as tonic etc. The present study determines the antiplasmodial effect of aqueous ethanolic seed extract against Chloroquine sensitive Plasmodium berghei berghei nk65 infection in Swiss albino mice. Based upon the acute toxicity data three different doses (100, 200, 400 mg/kg body weight of the plant extract was chosen to study the blood schizonticidal activity in early infection and in established infection and was compared with chloroquine. The Prophylactic activity was also assessed and compared with pyrimethamine. No mortality was observed in acute toxicity study however, above the dose of 1000 mg/kg animals showed the lethargic behaviour. In early infection, and in established infection the doses (100-400 mg/kg b.wt was found to cause significant (P<0.001 suppression of infection in a dose dependent manner as compared to control. Although, the activity was lower than standard chloroquine. Similarly, the extract at all the doses caused the suppression in repository activity but was lower than pyrimethamine. The mean survival time was also increased in mice by 14 and 17 days at the doses of 200 and 400 mg/kg respectively, whereas the control group sustained only for 7 days. Thus, the seed extract showed the effectiveness against plasmodium infection.

  15. Artemisinin-Resistant Plasmodium falciparum Malaria.

    Science.gov (United States)

    Fairhurst, Rick M; Dondorp, Arjen M

    2016-06-01

    For more than five decades, Southeast Asia (SEA) has been fertile ground for the emergence of drug-resistant Plasmodium falciparum malaria. After generating parasites resistant to chloroquine, sulfadoxine, pyrimethamine, quinine, and mefloquine, this region has now spawned parasites resistant to artemisinins, the world's most potent antimalarial drugs. In areas where artemisinin resistance is prevalent, artemisinin combination therapies (ACTs)-the first-line treatments for malaria-are failing fast. This worrisome development threatens to make malaria practically untreatable in SEA, and threatens to compromise global endeavors to eliminate this disease. A recent series of clinical, in vitro, genomics, and transcriptomics studies in SEA have defined in vivo and in vitro phenotypes of artemisinin resistance, identified its causal genetic determinant, explored its molecular mechanism, and assessed its clinical impact. Specifically, these studies have established that artemisinin resistance manifests as slow parasite clearance in patients and increased survival of early-ring-stage parasites in vitro; is caused by single nucleotide polymorphisms in the parasite's K13 gene, is associated with an upregulated "unfolded protein response" pathway that may antagonize the pro-oxidant activity of artemisinins, and selects for partner drug resistance that rapidly leads to ACT failures. In SEA, clinical studies are urgently needed to monitor ACT efficacy where K13 mutations are prevalent, test whether new combinations of currently available drugs cure ACT failures, and advance new antimalarial compounds through preclinical pipelines and into clinical trials. Intensifying these efforts should help to forestall the spread of artemisinin and partner drug resistance from SEA to sub-Saharan Africa, where the world's malaria transmission, morbidity, and mortality rates are highest.

  16. Mosquito transmission of wild turkey malaria, Plasmodium hermani.

    Science.gov (United States)

    Young, M D; Nayar, J K; Forrester, D J

    1977-04-01

    Culex nigripalpus experimentally transmitted Plasmodium hermani, a plasmodium of wild turkeys (Meleagris gallopavo) in Florida. The mosquitoes were infected by feeding upon blood induced parasitemias in domestic turkey poults. The resulting sporozoites, transmitted by either mosquito bites or injection, produced malaria infections in domestic poults.

  17. 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,

  18. 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,

  19. Deaths due to Plasmodium knowlesi malaria in Sabah, Malaysia: association with reporting as Plasmodium malariae and delayed parenteral artesunate

    Directory of Open Access Journals (Sweden)

    Rajahram Giri S

    2012-08-01

    Full Text Available Abstract Background The simian parasite Plasmodium knowlesi is recognized as a common cause of severe and fatal human malaria in Sabah, Malaysia, but is morphologically indistinguishable from and still commonly reported as Plasmodium malariae, despite the paucity of this species in Sabah. Since December 2008 Sabah Department of Health has recommended intravenous artesunate and referral to a general hospital for all severe malaria cases of any species. This paper reviews all malaria deaths in Sabah subsequent to the introduction of these measures. Reporting of malaria deaths in Malaysia is mandatory. Methods Details of reported malaria deaths during 2010-2011 were reviewed to determine the proportion of each Plasmodium species. Demographics, clinical presentations and management of severe malaria caused by each species were compared. Results Fourteen malaria deaths were reported, comprising seven Plasmodium falciparum, six P. knowlesi and one Plasmodium vivax (all PCR-confirmed. Of the six P. knowlesi deaths, five were attributable to knowlesi malaria and one was attributable to P. knowlesi-associated enterobacter sepsis. Patients with directly attributable P. knowlesi deaths (N = 5 were older than those with P. falciparum (median age 51 [IQR 50-65] vs 22 [IQR 9-55] years, p = 0.06. Complications in fatal P. knowlesi included respiratory distress (N = 5, 100%, hypotension (N = 4, 80%, and renal failure (N = 4, 80%. All patients with P. knowlesi were reported as P. malariae by microscopy. Only two of five patients with severe knowlesi malaria on presentation received immediate parenteral anti-malarial treatment. The patient with P. vivax-associated severe illness did not receive parenteral treatment. In contrast six of seven patients with severe falciparum malaria received immediate parenteral treatment. Conclusion Plasmodium knowlesi was responsible, either directly or through gram-negative bacteraemia, for almost half of

  20. Myocarditis associated with Plasmodium vivax malaria: a case report

    Directory of Open Access Journals (Sweden)

    Ana Maria Revoredo da Silva Ventura

    2014-12-01

    Full Text Available Malaria remains a major public health problem in Brazil where Plasmodium vivax is the predominant species, responsible for 82% of registered cases in 2013. Though benign, P. vivax infection may sometimes evolve with complications and a fatal outcome. Here, we report a severe case of P. vivax malaria in a 35-year-old Brazilian man from a malaria endemic area, who presented with reversible myocarditis.

  1. 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 ...

  2. Expression of cytosolic peroxiredoxins in Plasmodium berghei ookinetes is regulated by environmental factors in the mosquito bloodmeal.

    Directory of Open Access Journals (Sweden)

    Benjamin A Turturice

    2013-01-01

    Full Text Available The Plasmodium ookinete develops over several hours in the bloodmeal of its mosquito vector where it is exposed to exogenous stresses, including cytotoxic reactive oxygen species (ROS. How the parasite adapts to these challenging conditions is not well understood. We have systematically investigated the expression of three cytosolic antioxidant proteins, thioredoxin-1 (Trx-1, peroxiredoxin-1 (TPx-1, and 1-Cys peroxiredoxin (1-Cys Prx, in developing ookinetes of the rodent parasite Plasmodium berghei under various growth conditions. Transcriptional profiling showed that tpx-1 and 1-cys prx but not trx-1 are more strongly upregulated in ookinetes developing in the mosquito bloodmeal when compared to ookinetes growing under culture conditions. Confocal immunofluorescence imaging revealed comparable expression patterns on the corresponding proteins. 1-Cys Prx in particular exhibited strong expression in mosquito-derived ookinetes but was not detectable in cultured ookinetes. Furthermore, ookinetes growing in culture upregulated tpx-1 and 1-cys prx when challenged with exogenous ROS in a dose-dependent fashion. This suggests that environmental factors in the mosquito bloodmeal induce upregulation of cytosolic antioxidant proteins in Plasmodium ookinetes. We found that in a parasite line lacking TPx-1 (TPx-1KO, expression of 1-Cys Prx occurred significantly earlier in mosquito-derived TPx-1KO ookinetes when compared to wild type (WT ookinetes. The protein was also readily detectable in cultured TPx-1KO ookinetes, indicating that 1-Cys Prx at least in part compensates for the loss of TPx-1 in vivo. We hypothesize that this dynamic expression of the cytosolic peroxiredoxins reflects the capacity of the developing Plasmodium ookinete to rapidly adapt to the changing conditions in the mosquito bloodmeal. This would significantly increase its chances of survival, maturation and subsequent escape. Our results also emphasize that environmental conditions

  3. Characterization of Plasmodium developmental transcriptomes in Anopheles gambiae midgut reveals novel regulators of malaria transmission.

    Science.gov (United States)

    Akinosoglou, Karolina A; Bushell, Ellen S C; Ukegbu, Chiamaka Valerie; Schlegelmilch, Timm; Cho, Jee-Sun; Redmond, Seth; Sala, Katarzyna; Christophides, George K; Vlachou, Dina

    2015-02-01

    The passage through the mosquito is a major bottleneck for malaria parasite populations and a target of interventions aiming to block disease transmission. Here, we used DNA microarrays to profile the developmental transcriptomes of the rodent malaria parasite Plasmodium berghei in vivo, in the midgut of Anopheles gambiae mosquitoes, from parasite stages in the midgut blood bolus to sporulating oocysts on the basal gut wall. Data analysis identified several distinct transcriptional programmes encompassing genes putatively involved in developmental processes or in interactions with the mosquito. At least two of these programmes are associated with the ookinete development that is linked to mosquito midgut invasion and establishment of infection. Targeted disruption by homologous recombination of two of these genes resulted in mutant parasites exhibiting notable infection phenotypes. GAMER encodes a short polypeptide with granular localization in the gametocyte cytoplasm and shows a highly penetrant loss-of-function phenotype manifested as greatly reduced ookinete numbers, linked to impaired male gamete release. HADO encodes a putative magnesium phosphatase with distinctive cortical localization along the concave ookinete periphery. Disruption of HADO compromises ookinete development leading to significant reduction of oocyst numbers. Our data provide important insights into the molecular framework underpinning Plasmodium development in the mosquito and identifies two genes with important functions at initial stages of parasite development in the mosquito midgut.

  4. Plasmodium vivax cerebral malaria complicated with venous sinus thrombosis in Colombia

    Institute of Scientific and Technical Information of China (English)

    Miguel A Pinzn; Juan C Pineda; Fernando Rosso; Masaru Shinchi; Fabio Bonilla-Abada

    2013-01-01

    Complicated malaria is usually due to Plasmodium falciparum. Nevertheless, Plasmodium vivax is infrequently related with life-threatening complications. Few cases have been reported of severe Plasmodium vivax infection, and most of them from Southeast Asia and India. We report the first case of cerebral malaria due to Plasmodium vivax in Latin America, complicated with sagittal sinus thrombosis and confirmed by a molecular method.

  5. Combating multidrug-resistant Plasmodium falciparum malaria.

    Science.gov (United States)

    Thu, Aung Myint; Phyo, Aung Pyae; Landier, Jordi; Parker, Daniel M; Nosten, François H

    2017-08-01

    Over the past 50 years, Plasmodium falciparum has developed resistance against all antimalarial drugs used against it: chloroquine, sulphadoxine-pyrimethamine, quinine, piperaquine and mefloquine. More recently, resistance to the artemisinin derivatives and the resulting failure of artemisinin-based combination therapy (ACT) are threatening all major gains made in malaria control. Each time resistance has developed progressively, with delayed clearance of parasites first emerging only in a few regions, increasing in prevalence and geographic range, and then ultimately resulting in the complete failure of that antimalarial. Drawing from this repeated historical chain of events, this article presents context-specific approaches for combating drug-resistant P. falciparum malaria. The approaches begin with a context of drug-sensitive parasites and focus on the prevention of the emergence of drug resistance. Next, the approaches address a scenario in which resistance has emerged and is increasing in prevalence and geographic extent, with interventions focused on disrupting transmission through vector control, early diagnosis and treatment, and the use of new combination therapies. Elimination is also presented as an approach for addressing the imminent failure of all available antimalarials. The final drug resistance context presented is one in which all available antimalarials have failed; leaving only personal protection and the use of new antimalarials (or new combinations of antimalarials) as a viable strategy for dealing with complete resistance. All effective strategies and contexts require a multipronged, holistic approach. © 2017 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

  6. 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...

  7. 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...

  8. An essential role of the basal body protein SAS-6 in Plasmodium male gamete development and malaria transmission.

    Science.gov (United States)

    Marques, Sara R; Ramakrishnan, Chandra; Carzaniga, Raffaella; Blagborough, Andrew M; Delves, Michael J; Talman, Arthur M; Sinden, Robert E

    2015-02-01

    Gametocytes are the sole Plasmodium parasite stages that infect mosquitoes; therefore development of functional gametes is required for malaria transmission. Flagellum assembly of the Plasmodium male gamete differs from that of most other eukaryotes in that it is intracytoplasmic but retains a key conserved feature: axonemes assemble from basal bodies. The centriole/basal body protein SAS-6 normally regulates assembly and duplication of these organelles and its depletion causes severe flagellar/ciliary abnormalities in a diverse array of eukaryotes. Since basal body and flagellum assembly are intimately coupled to male gamete development in Plasmodium, we hypothesized that SAS-6 disruption may cause gametogenesis defects and perturb transmission. We show that Plasmodium berghei sas6 knockouts display severely abnormal male gametogenesis presenting reduced basal body numbers, axonemal assembly defects and abnormal nuclear allocation. The defects in gametogenesis reduce fertilization and render Pbsas6 knockouts less infectious to mosquitoes. Additionally, we show that lack of Pbsas6 blocks transmission from mosquito to vertebrate host, revealing an additional yet undefined role in ookinete to sporulating oocysts transition. These findings underscore the vulnerability of the basal body/SAS-6 to malaria transmission blocking interventions.

  9. Accurate identification of the six human Plasmodium spp. causing imported malaria, including Plasmodium ovale wallikeri and Plasmodium knowlesi.

    Science.gov (United States)

    Calderaro, Adriana; Piccolo, Giovanna; Gorrini, Chiara; Rossi, Sabina; Montecchini, Sara; Dell'Anna, Maria Loretana; De Conto, Flora; Medici, Maria Cristina; Chezzi, Carlo; Arcangeletti, Maria Cristina

    2013-09-13

    Accurate identification of Plasmodium infections in non-endemic countries is of critical importance with regard to the administration of a targeted therapy having a positive impact on patient health and management and allowing the prevention of the risk of re-introduction of endemic malaria in such countries. Malaria is no longer endemic in Italy where it is the most commonly imported disease, with one of the highest rates of imported malaria among European non-endemic countries including France, the UK and Germany, and with a prevalence of 24.3% at the University Hospital of Parma. Molecular methods showed high sensitivity and specificity and changed the epidemiology of imported malaria in several non-endemic countries, highlighted a higher prevalence of Plasmodium ovale, Plasmodium vivax and Plasmodium malariae underestimated by microscopy and, not least, brought to light both the existence of two species of P. ovale (Plasmodium ovale curtisi and Plasmodium ovale wallikeri) and the infection in humans by Plasmodium knowlesi, otherwise not detectable by microscopy. In this retrospective study an evaluation of two real-time PCR assays able to identify P. ovale wallikeri, distinguishing it from P. ovale curtisi, and to detect P. knowlesi, respectively, was performed applying them on a subset of 398 blood samples belonging to patients with the clinical suspicion of malaria. These assays revealed an excellent analytical sensitivity and no cross-reactivity versus other Plasmodium spp. infecting humans, suggesting their usefulness for an accurate and complete diagnosis of imported malaria. Among the 128 patients with malaria, eight P. ovale curtisi and four P. ovale wallikeri infections were detected, while no cases of P. knowlesi infection were observed. Real-time PCR assays specific for P. ovale wallikeri and P. knowlesi were included in the panel currently used in the University Hospital of Parma for the diagnosis of imported malaria, accomplishing the goal of

  10. Plasmodium Cysteine Repeat Modular Proteins 3 and 4 are essential for malaria parasite transmission from the mosquito to the host

    Directory of Open Access Journals (Sweden)

    Mota Maria M

    2011-03-01

    Full Text Available Abstract Background The Plasmodium Cysteine Repeat Modular Proteins (PCRMP are a family of four conserved proteins of malaria parasites, that contain a number of motifs implicated in host-parasite interactions. Analysis of mutants of the rodent parasite Plasmodium berghei lacking expression of PCRMP1 or 2 showed that these proteins are essential for targeting of P. berghei sporozoites to the mosquito salivary gland and, hence, for transmission from the mosquito to the mouse. Methods In this work, the role of the remaining PCRMP family members, PCRMP3 and 4, has been investigated throughout the Plasmodium life cycle by generation and analysis of P. berghei gene deletion mutants, Δpcrmp3 and Δpcrmp4. The role of PCRMP members during the transmission and hepatic stages of the Plasmodium lifecycle has been evaluated by light- and electron microscopy and by analysis of liver stage development in HEPG2 cells in vitro and by infecting mice with mutant sporozoites. In addition, mice were immunized with live Δpcrmp3 and Δpcrmp4 sporozoites to evaluate their immunization potential as a genetically-attenuated parasite-based vaccine. Results Disruption of pcrmp3 and pcrmp4 in P. berghei revealed that they are also essential for transmission of the parasite through the mosquito vector, although acting in a distinct way to pbcrmp1 and 2. Mutants lacking expression of PCRMP3 or PCRMP4 show normal blood stage development and oocyst formation in the mosquito and develop into morphologically normal sporozoites, but these have a defect in egress from oocysts and do not enter the salivary glands. Sporozoites extracted from oocysts perform gliding motility and invade and infect hepatocytes but do not undergo further development and proliferation. Furthermore, the study shows that immunization with Δcrmp3 and Δcrmp4 sporozoites does not confer protective immunity upon subsequent challenge. Conclusions PCRMP3 and 4 play multiple roles during the Plasmodium life

  11. Chimpanzee malaria parasites related to Plasmodium ovale in Africa.

    Directory of Open Access Journals (Sweden)

    Linda Duval

    Full Text Available Since the 1970's, the diversity of Plasmodium parasites in African great apes has been neglected. Surprisingly, P. reichenowi, a chimpanzee parasite, is the only such parasite to have been molecularly characterized. This parasite is closely phylogenetically related to P. falciparum, the principal cause of the greatest malaria burden in humans. Studies of malaria parasites from anthropoid primates may provide relevant phylogenetic information, improving our understanding of the origin and evolutionary history of human malaria species. In this study, we screened 130 DNA samples from chimpanzees (Pan troglodytes and gorillas (Gorilla gorilla from Cameroon for Plasmodium infection, using cytochrome b molecular tools. Two chimpanzees from the subspecies Pan t. troglodytes presented single infections with Plasmodium strains molecularly related to the human malaria parasite P. ovale. These chimpanzee parasites and 13 human strains of P. ovale originated from a various sites in Africa and Asia were characterized using cytochrome b and cytochrome c oxidase 1 mitochondrial partial genes and nuclear ldh partial gene. Consistent with previous findings, two genetically distinct types of P. ovale, classical and variant, were observed in the human population from a variety of geographical locations. One chimpanzee Plasmodium strain was genetically identical, on all three markers tested, to variant P. ovale type. The other chimpanzee Plasmodium strain was different from P. ovale strains isolated from humans. This study provides the first evidence of possibility of natural cross-species exchange of P. ovale between humans and chimpanzees of the subspecies Pan t. troglodytes.

  12. Antimalarial and hepatoprotective effects of crude ethanolic extract of Lingzhi or Reishi medicinal mushroom, Ganoderma lucidum (W.Curt.:Fr.)P.Karst. (higher Basidiomycetes), in Plasmodium berghei-infected mice.

    Science.gov (United States)

    Oluba, Olarewaju M; Olusola, Augustine O; Fagbohunka, Bamidele S; Onyeneke, E

    2012-01-01

    This study was aimed at investigating the in vivo antimalarial activity (using some biochemical indices) of crude aqueous extracts of the fruiting bodies of Ganoderma lucidum, a mushroom with well-established medicinal properties. A rodent malaria parasite, Plasmodium berghei (1 × 107), was inoculated intraperitoneally into Swiss albino mice. The test groups were administered G. lucidum extract and chloroquine (CQ, as standard drug), while the control groups were administered the same amount of distilled water by an intragastric tube once daily. The antimalarial activity of the extract was investigated from the suppressive, curative, and prophylactic effects of the extract on parasite growth. Serum aminotransferases (AST and ALT), alkaline phosphatase (ALP), and gamma glutamine transpeptidase (γ-GT) levels monitored following the 4-day suppressive test were significantly reduced, with a corresponding significant increase in the livers of mice treated with the extract compared with infected untreated mice. The results obtained from this study provide scientific justification in an animal model of malaria that an ethanolic extract of G. lucidum possesses potent antimalarial activity and also could help ameliorate the attendant Plasmodium-induced liver damage due to malarial infection.

  13. [Plasmodium falciparum malaria: epidemiology and clinical features at Tarapoto Hospital].

    Science.gov (United States)

    Calderon, J; Rodriguez, J; Romero, D

    1997-01-01

    A retrospective study was conducted of the clinical records of 41 patients discharged from a hospital in Tarapoto, Peru, between August 1992 and June 1996 following treatment for Plasmodium falciparum malaria. Patients ranged in age from 18 to 65 years; 25 were male. The cases were uniformly distributed throughout the year. The duration of illness averaged 11 days. At admission, 40 patients had fever, 36 had shaking chills, 29 had headache, 21 had nausea and vomiting, 21 had hyporexia, 15 had pallor, and 13 had splenomegaly. 3 of the 16 women were pregnant. 7 patients reported a history of malaria. The admission diagnosis was malaria in 33 cases. 31 patients were treated with chloroquine; 18 were subsequently treated with pyrimethamine-sulfadoxin and 1 received doxycycline. No cases of grave illness or death occurred. The increasing presence of Plasmodium falciparum malaria in the Peruvian lowlands should promote review of the adequacy of control programs.

  14. Mosquito Vectors and the Globalization of Plasmodium falciparum Malaria.

    Science.gov (United States)

    Molina-Cruz, Alvaro; Zilversmit, Martine M; Neafsey, Daniel E; Hartl, Daniel L; Barillas-Mury, Carolina

    2016-11-23

    Plasmodium falciparum malaria remains a devastating public health problem. Recent discoveries have shed light on the origin and evolution of Plasmodium parasites and their interactions with their vertebrate and mosquito hosts. P. falciparum malaria originated in Africa from a single horizontal transfer between an infected gorilla and a human, and became global as the result of human migration. Today, P. falciparum malaria is transmitted worldwide by more than 70 different anopheline mosquito species. Recent studies indicate that the mosquito immune system can be a barrier to malaria transmission and that the P. falciparum Pfs47 gene allows the parasite to evade mosquito immune detection. Here, we review the origin and globalization of P. falciparum and integrate this history with analysis of the biology, evolution, and dispersal of the main mosquito vectors. This new perspective broadens our understanding of P. falciparum population structure and the dispersal of important parasite genetic traits.

  15. Mitosis in the Human Malaria Parasite Plasmodium falciparum ▿

    Science.gov (United States)

    Gerald, Noel; Mahajan, Babita; Kumar, Sanjai

    2011-01-01

    Malaria is caused by intraerythrocytic protozoan parasites belonging to Plasmodium spp. (phylum Apicomplexa) that produce significant morbidity and mortality, mostly in developing countries. Plasmodium parasites have a complex life cycle that includes multiple stages in anopheline mosquito vectors and vertebrate hosts. During the life cycle, the parasites undergo several cycles of extreme population growth within a brief span, and this is critical for their continued transmission and a contributing factor for their pathogenesis in the host. As with other eukaryotes, successful mitosis is an essential requirement for Plasmodium reproduction; however, some aspects of Plasmodium mitosis are quite distinct and not fully understood. In this review, we will discuss the current understanding of the architecture and key events of mitosis in Plasmodium falciparum and related parasites and compare them with the traditional mitotic events described for other eukaryotes. PMID:21317311

  16. Surface antigens and virulence in Plasmodium falciparum malaria

    OpenAIRE

    Normark, Johan

    2008-01-01

    Plasmodium falciparum is an intracellular protozoan that may cause severe forms of malaria. It is a major world health hazard and reaps the highest toll among the children and pregnant mothers of the developing world. An Anopheles mosquito vector injects the pathogen when taking a blood meal. After multiplication in cells of the liver, the parasite escapes and infects red blood cells in a cyclic manner and this is when the clinical manifestations of malaria as a disease beco...

  17. Evidência da ação antiparasitária da azitromicina na infecção experimental de camundongos pelo Plasmodium berghei

    Directory of Open Access Journals (Sweden)

    Gakiya Erika

    2001-01-01

    Full Text Available A azitromicina debelou a infecção experimental de camundongos pelo Plasmodium berghei quando administrada, pela via oral e durante 28 dias, na dose de 100mg/kg, iniciada no mesmo dia em que os animais foram infectados. Mediante uso de 10mg/kg houve insucesso. Os resultados obtidos suscitam investigações complementares sobre a referida atividade antiparasitária desse medicamento.

  18. Teste de hemaglutinação na sorologia da malária humana empregando hemácias parasitadas pelo Plasmodium berghei

    Directory of Open Access Journals (Sweden)

    Maria Carmen Arroyo Sanchez-Ruiz

    1985-06-01

    Full Text Available Foi padronizado um teste de hemaglutinação para a sorologia da malária humana, com reagente constituído de suspensão de hemácias de camundongos infectadas pelo Plasmodium berghei e preservadas por fixação aldeídica. Em pacientes com parasitemia por P. falciparum ou P. vivax obteve-se uma sensibilidade de 98,9% nos 88 casos estudados, o teste apresentando títulos entre 40 e 640. Para o grupo de 476 soros de indivíduos não-maláricos, obteve-se uma especificidade de 96,0%. O teste apresentou elevada reprodutibilidade, mesmo para diferentes lotes de antígenos. Nos 200 soros, obtidos ao acaso, de indivíduos de área endêmica, o teste apresentou positividade de 48,5%, contra 88,0% do teste de imunofluorescência-IgG. A baixa positividade pode ser devida a que o teste de hemaglutinação detecta anticorpos IgM. Após tratamento com 2-mercaptoetanol, todos os soros de pacientes com parasitemia tornaram-se não reagentes. Em relação ao teste de imunofluorescência-IgG, o teste de hemaglutinação apresentou índice de co-positívidade de 0,989 para os soros de maláricos com parasitemia. Para os soros de não-maláricos o teste de hemaglutinação apresentou índice de co-negatividade de 0,969. Por outro lado, no grupo de soros de área endêmica, o índice de co-positividade foi de 0,528 e o de co-negatividade, de 0,833.A hemagglutination test is described for human malaria serodiagnosis with aldehyde-fixed Plasmodium berghei infected mouse erythrocytes. In patients with a P. falciparum or P. vivax patent parasitemia positive results were seen in 98.9% ofthe 88 cases tested. Titres rangedfrom 40 to 640. A 96.0% specificity wasfoundfor 476 non-malarialpatients. A close reproducibility was observed forthe test, even for dijferent reagent batches. The test was positive in 48.5% of 200 residents in malaria endemic areas, taken at random. These subjects showed 88.0% positivity of the IgG-immunofluorescence test. This lower positivity for

  19. Plasmodium vivax malaria among pregnant women in Eastern Sudan

    Directory of Open Access Journals (Sweden)

    Duria Abdulwhab Rayis

    2016-06-01

    Full Text Available Objective: To determine the epidemiology of malaria [especially Plasmodium vivax (P. vivax] among pregnant women in Eastern Sudan. Methods: A cross sectional study was conducted in the antenatal care of New Halfa hospital, Eastern Sudan to investigate the prevalence, manifestations and determinants of malaria (especially P. vivax among pregnant women. Results: Out of 2 378 pregnant women, there were 48 (2.0% and 36 (1.5% Plasmodium falciparum (P. falciparum and P. vivax infection, respectively. There was no significant difference in the age, parity, gestational age between women with malaria and healthy controls. The mean ± SD of the temperature was significantly higher in patients with P. vivax than in patient with P. falciparum malaria [(38.6 ± 0.7 °C vs. (38.1 ± 0.6 °C, P = 0.001]. Patients with P. vivax malaria had slightly (not reach statistical significance lower hemoglobin level compared with P. falciparum malaria and healthy controls. The geometric parasite count showed no significant difference between patients with P. vivax and P. falciparum malaria infections (12 189.9 vs. 9 755.1 trophozoite/µL, P = 0.356. Conclusions: P. vivax malaria is an existing health problem in Eastern Sudan. Further research is also needed.

  20. The evolution and putative function of phosducin-like proteins in the malaria parasite Plasmodium.

    Science.gov (United States)

    Putonti, Catherine; Quach, Bryan; Kooistra, Rachel L; Kanzok, Stefan M

    2013-01-01

    Ubiquitous to the proteomes of all living species is the presence of proteins containing the thioredoxin (Trx)-domain. The best characterized Trx-domain containing proteins include the enzymes involved in cellular redox metabolism facilitated by their cysteine-containing active site. But not all members of the Trx-fold superfamily exhibit this catalytic motif, e.g., the phosducin-like (PhLP) family of proteins. Genome sequencing efforts have uncovered new Trx-domain containing proteins, and their redox activity and cellular functions have yet to be determined. The genome of the malaria parasite Plasmodium contains multiple thioredoxins and thioredoxin-like proteins which are of considerable interest given their role in the parasite's antioxidant defense. While adaptations within the Trx-domain have been studied, primarily with respect to redox active structures, PhLP proteins have not been examined. Using the uncharacterized phosducin-like protein from Plasmodium berghei PhLP-1, we investigated the evolution of PhLP proteins across all branches of the tree of life. As a result of our analysis, we have discovered the presence of two additional PhLP proteins in Plasmodium, PhLP-2 and PhLP-3. Sequence homology with annotated PhLP proteins in other species confirms that the Plasmodium PhLP-2 and PhLP-3 belong to the PhLP family of proteins. Furthermore, as a result of our analysis we hypothesize that the PhLP-2 thioredoxin was lost over time given its absence from higher-order eukaryotes. Probing deeper into the putative function of these proteins, inspection of the active sites indicate that PbPhLP-1 and PbPhLP-2 may be redox active while PbPhLP-3 is very likely not. The results of this phylogenetic study provide insight into the emergence of this family of Trx-domain containing proteins.

  1. Chitinase 3-like 1 is induced by Plasmodium falciparum malaria and predicts outcome of cerebral malaria and severe malarial anaemia in a case-control study of African children.

    Science.gov (United States)

    Erdman, Laura K; Petes, Carlene; Lu, Ziyue; Dhabangi, Aggrey; Musoke, Charles; Cserti-Gazdewich, Christine M; Lee, Chun Geun; Liles, Wayne Conrad; Elias, Jack A; Kain, Kevin C

    2014-07-21

    Severe and fatal malaria are associated with dysregulated host inflammatory responses to infection. Chitinase 3-like 1 (CHI3L1) is a secreted glycoprotein implicated in regulating immune responses. Expression and function of CHI3L1 in malaria infection were investigated. Plasma levels of CHI3L1 were quantified in a case-control study of Ugandan children presenting with Plasmodium falciparum malaria. CHI3L1 levels were compared in children with uncomplicated malaria (UM; n = 53), severe malarial anaemia (SMA; n = 59) and cerebral malaria (CM; n = 44) using the Kruskall Wallis-test, and evaluated for utility in predicting fatal (n = 23) versus non-fatal (n = 80) outcomes in severe disease using the Mann Whitney U test, receiver operating characteristic curves, and combinatorial analysis. Co-culture of P. falciparum with human peripheral blood mononuclear cells and the Plasmodium berghei ANKA experimental model of cerebral malaria were used to examine the role of CHI3L1 in severe malaria. In children presenting with falciparum malaria, CHI3L1 levels were increased in SMA and CM versus UM (p Plasmodium falciparum stimulated CHI3L1 production by human peripheral blood mononuclear cells in vitro. CHI3L1 was increased in plasma and brain tissue in experimental cerebral malaria, but targeted Chi3l1 deletion did not alter cytokine production or survival in this model. These data suggest that plasma CHI3L1 measured at presentation correlates with malaria severity and predicts outcome in paediatric SMA and CM, but do not support a causal role for CHI3L1 in cerebral malaria pathobiology in the model tested.

  2. 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.

  3. Naturally acquired immunity to Plasmodium falciparum malaria in Africa

    DEFF Research Database (Denmark)

    Hviid, Lars

    2005-01-01

    protective immunity to P. falciparum malaria is acquired following natural exposure to the parasites is beginning to emerge, not least thanks to studies that have combined clinical and epidemiological data with basic immunological research. This framework involves IgG with specificity for clonally variant......Infection by Plasmodium falciparum parasites can lead to substantial protective immunity to malaria, and available evidence suggest that acquisition of protection against some severe malaria syndromes can be fairly rapid. Although these facts have raised hopes that the development of effective...

  4. Genome-scale comparison of expanded gene families in Plasmodium ovale wallikeri and Plasmodium ovale curtisi with Plasmodium malariae and with other Plasmodium species

    KAUST Repository

    Ansari, Hifzur Rahman

    2016-07-05

    Malaria in humans is caused by six species of Plasmodium parasites, of which the nuclear genome sequences for the two Plasmodium ovale spp., P. ovale curtisi and P. ovale wallikeri, and Plasmodium malariae have not yet been analyzed. Here we present an analysis of the nuclear genome sequences of these three parasites, and describe gene family expansions therein. Plasmodium ovale curtisi and P. ovale wallikeri are genetically distinct but morphologically indistinguishable and have sympatric ranges through the tropics of Africa, Asia and Oceania. Both P. ovale spp. show expansion of the surfin variant gene family, and an amplification of the Plasmodium interspersed repeat (pir) superfamily which results in an approximately 30% increase in genome size. For comparison, we have also analyzed the draft nuclear genome of P. malariae, a malaria parasite causing mild malaria symptoms with a quartan life cycle, long-term chronic infections, and wide geographic distribution. Plasmodium malariae shows only a moderate level of expansion of pir genes, and unique expansions of a highly diverged transmembrane protein family with over 550 members and the gamete P25/27 gene family. The observed diversity in the P. ovale wallikeri and P. ovale curtisi surface antigens, combined with their phylogenetic separation, supports consideration that the two parasites be given species status.

  5. Optimal strategy for controlling the spread of Plasmodium Knowlesi malaria: Treatment and culling

    Science.gov (United States)

    Abdullahi, Mohammed Baba; Hasan, Yahya Abu; Abdullah, Farah Aini

    2015-05-01

    Plasmodium Knowlesi malaria is a parasitic mosquito-borne disease caused by a eukaryotic protist of genus Plasmodium Knowlesi transmitted by mosquito, Anopheles leucosphyrus to human and macaques. We developed and analyzed a deterministic Mathematical model for the transmission of Plasmodium Knowlesi malaria in human and macaques. The optimal control theory is applied to investigate optimal strategies for controlling the spread of Plasmodium Knowlesi malaria using treatment and culling as control strategies. The conditions for optimal control of the Plasmodium Knowlesi malaria are derived using Pontryagin's Maximum Principle. Finally, numerical simulations suggested that the combination of the control strategies is the best way to control the disease in any community.

  6. Artemether-lumefantrine treatment of uncomplicated Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Kofoed, Poul-Erik

    2015-01-01

    -lumefantrine for uncomplicated Plasmodium falciparum malaria, to define therapeutic day 7 lumefantrine concentrations and identify patient factors that substantially alter these concentrations. A systematic review of PubMed, Embase, Google Scholar, ClinicalTrials.gov and conference proceedings identified all relevant studies...

  7. Plasmodium vivax and Plasmodium falciparum are Common Malaria Species in Pakistan

    Directory of Open Access Journals (Sweden)

    Tauseef Ahmad

    2016-06-01

    Full Text Available The microbes have a diverse nature, it makes human laugh and cry. Some microbes are fruitful for humans while others are harmful. Infectious diseases are a key problem in the modern world. In the last few decades, million of peoples have died from different diseases, including bacterial, viral, fungal, parasitic, etc. Among these diseases, malaria is one of the major health problems for developing countries including Pakistan. This study was undertaken to provide baseline information about the prevalence of malaria, species distribution and to contribute to the data regarding epidemiology in Pakistan. For a collection of literature, the electronic search engine was used, using different key words i.e. prevalence, species distribution, epidemiology of malaria in Pakistan, etc. The time frame of the obtained articles was from 2000 to 2014. The two species of malaria Plasmodium vivax and Plasmodium falciparum are common in Pakistan. [Biomed Res Ther 2016; 3(6.000: 666-672

  8. [From malaria parasite point of view--Plasmodium falciparum evolution].

    Science.gov (United States)

    Zerka, Agata; Kaczmarek, Radosław; Jaśkiewicz, Ewa

    2015-12-31

    Malaria is caused by infection with protozoan parasites belonging to the genus Plasmodium, which have arguably exerted the greatest selection pressure on humans in the history of our species. Besides humans, different Plasmodium parasites infect a wide range of animal hosts, from marine invertebrates to primates. On the other hand, individual Plasmodium species show high host specificity. The extraordinary evolution of Plasmodium probably began when a free-living red algae turned parasitic, and culminated with its ability to thrive inside a human red blood cell. Studies on the African apes generated new data on the evolution of malaria parasites in general and the deadliest human-specific species, Plasmodium falciparum, in particular. Initially, it was hypothesized that P. falciparum descended from the chimpanzee malaria parasite P. reichenowi, after the human and the chimp lineage diverged about 6 million years ago. However, a recently identified new species infecting gorillas, unexpectedly showed similarity to P. falciparum and was therefore named P. praefalciparum. That finding spurred an alternative hypothesis, which proposes that P. falciparum descended from its gorilla rather than chimp counterpart. In addition, the gorilla-to-human host shift may have occurred more recently (about 10 thousand years ago) than the theoretical P. falciparum-P. reichenowi split. One of the key aims of the studies on Plasmodium evolution is to elucidate the mechanisms that allow the incessant host shifting and retaining the host specificity, especially in the case of human-specific species. Thorough understanding of these phenomena will be necessary to design effective malaria treatment and prevention strategies.

  9. Molecular characterization and phylogenetic analysis of Plasmodium vivax, Plasmodium falciparum, Plasmodium ovale, Plasmodium malariae and Plasmodium cynomolgi

    National Research Council Canada - National Science Library

    Chatterjee, Soumendranath; Mukhopadhyay, Priyanka; Bandyopadhyay, Raktima; Dhal, Paltu; Biswal, Debraj; Bandyopadhyay, Prabir Kumar

    18S ribosomal RNA gene sequences of different species of Plasmodium were aligned and analyzed to determine the molecular diversity among different species of Plasmodium. AT content of P. cynomolgi, P. ovale, P. falciparum, P. vivax and P...

  10. 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....

  11. [Monkey malaria (Plasmodium knowlesi infection) after travelling to Thailand].

    Science.gov (United States)

    Kroidl, Inge; Seilmaier, Michael; Berens-Riha, Nicole; Bretzel, Gisela; Wendtner, Clemens; Löscher, Thomas

    2015-05-01

    A case of malaria caused by Plasmodium knowlesi is described in a 52-year-old female German traveler after returning from Thailand. P. knowlesi is a parasite of macaques in Southeast Asia and has been recognized in recent years as an important and probably increasing cause of human malaria in some areas. At least 16 cases in international travelers have been published so far. This includes four cases imported to Germany. All German patients visited forested areas in Southern Thailand inhabited by the natural monkey host prior to their illness. Most cases diagnosed in endemic areas present as mild disease. However in some patients P. knowlesi may take a severe and life-threatening course. Diagnosis is usually is based on microscopy whereas rapid tests are not reliable. However, microscopic differentiation of P. knowlesi from other plasmodium species (eg, P. malariae, P. falciparum) is difficult, especially when parasitemia is low. Thus PCR methods are required for definite species determination. Changing endemicity as well as changing tourism patterns such as the trend towards eco-tourism might increase the risk of infection for travelers even in areas which are considered as low endemic for malaria. Malaria has to be considered in all febrile patients returning from endemic areas. In Southeast Asia this has to include Plasmodium knowlesi infection. Especially if microscopy suggests P. falciparum/P. malariae double infection, or when results indicate P. malariae but the clinical presentation differs from that of quartan malaria (eg, daily fever), diagnostic procedures for P. knowlesi should be initiated. Currently available rapid diagnostic tests are not reliable for the detection of P. knowlesi. The definite diagnosis of P. knowlesi infection usually requires PCR techniques Changing tourism patterns such as the trend towards eco-tourism might increase the risk of infection for travelers even in low prevalence areas. © Georg Thieme Verlag KG Stuttgart · New York.

  12. RIFINs are adhesins implicated in severe Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Goel, Suchi; Palmkvist, Mia; Moll, Kirsten

    2015-01-01

    Rosetting is a virulent Plasmodium falciparum phenomenon associated with severe malaria. Here we demonstrate that P. falciparum–encoded repetitive interspersed families of polypeptides (RIFINs) are expressed on the surface of infected red blood cells (iRBCs), where they bind to RBCs—preferentiall......Rosetting is a virulent Plasmodium falciparum phenomenon associated with severe malaria. Here we demonstrate that P. falciparum–encoded repetitive interspersed families of polypeptides (RIFINs) are expressed on the surface of infected red blood cells (iRBCs), where they bind to RBCs......—preferentially of blood group A—to form large rosettes and mediate microvascular binding of iRBCs. We suggest that RIFINs have a fundamental role in the development of severe malaria and thereby contribute to the varying global distribution of ABO blood groups in the human population....

  13. The genome of the simian and human malaria parasite Plasmodium knowlesi

    DEFF Research Database (Denmark)

    Pain, A; Böhme, U; Berry, A E

    2008-01-01

    Plasmodium knowlesi is an intracellular malaria parasite whose natural vertebrate host is Macaca fascicularis (the 'kra' monkey); however, it is now increasingly recognized as a significant cause of human malaria, particularly in southeast Asia. Plasmodium knowlesi was the first malaria parasite ...

  14. Protection of renal function by four selected plant extracts during Plasmodium berghei infection

    OpenAIRE

    Adewale Adetutu; Olubukola Sinbad Olorunnisola; Kazeem Iyanda

    2015-01-01

    Background: Weakening of renal function from reactive oxygen species generated during malaria infection is one of the prominent causes of death in prevalent regions. The potential toxicity of free radical generated by malaria parasites are counteracted by a large number of cytoprotective phytochemicals. Therefore, this study examined the influence of extracts of five selected antimalarial plants (Azadirachta indica, Parquetina nigrescens, Citrus paradisi, and Khaya senigalensis) on reduction ...

  15. Plasmodium malariae and P. ovale genomes provide insights into malaria parasite evolution

    Science.gov (United States)

    Rutledge, Gavin G.; Böhme, Ulrike; Sanders, Mandy; Reid, Adam J.; Cotton, James A.; Maiga-Ascofare, Oumou; Djimdé, Abdoulaye A.; Apinjoh, Tobias O.; Amenga-Etego, Lucas; Manske, Magnus; Barnwell, John W.; Renaud, François; Ollomo, Benjamin; Prugnolle, Franck; Anstey, Nicholas M.; Auburn, Sarah; Price, Ric N.; McCarthy, James S.; Kwiatkowski, Dominic P.; Newbold, Chris I.; Berriman, Matthew; Otto, Thomas D.

    2017-01-01

    Elucidation of the evolutionary history and interrelatedness of Plasmodium species that infect humans has been hampered by a lack of genetic information for three human-infective species: P. malariae and two P. ovale species (P. o. curtisi and P. o. wallikeri)1. These species are prevalent across most regions in which malaria is endemic2,3 and are often undetectable by light microscopy4, rendering their study in human populations difficult5. The exact evolutionary relationship of these species to the other human-infective species has been contested6,7. Using a new reference genome for P. malariae and a manually curated draft P. o. curtisi genome, we are now able to accurately place these species within the Plasmodium phylogeny. Sequencing of a P. malariae relative that infects chimpanzees reveals similar signatures of selection in the P. malariae lineage to another Plasmodium lineage shown to be capable of colonization of both human and chimpanzee hosts. Molecular dating suggests that these host adaptations occurred over similar evolutionary timescales. In addition to the core genome that is conserved between species, differences in gene content can be linked to their specific biology. The genome suggests that P. malariae expresses a family of heterodimeric proteins on its surface that have structural similarities to a protein crucial for invasion of red blood cells. The data presented here provide insight into the evolution of the Plasmodium genus as a whole. PMID:28117441

  16. Modulation of Lipoprotein Cholesterol Levels in Plasmodium berghei Malarial Infection by Crude Aqueous Extract of Ganoderma lucidum

    Directory of Open Access Journals (Sweden)

    Olarewaju M. Oluba

    2012-01-01

    Full Text Available In this study, attempt is made to establish changes in serum and liver lipoprotein cholesterols accompanying Plasmodium berghei malarial infection in mice treated with aqueous extract of Ganoderma lucidum at 100, 250, and 500 mg/kg body weight in comparison with 15 mg/kg chloroquine (CQ. Significant increases in all the lipoprotein fractions were observed in infected untreated mice compared with normal control mice. Treatment with 100 and 250 mg/kg G. lucidum extract produced significant reduction in serum total cholesterol (TC and low-density cholesterol (LDL-C contents compared with 500 mg/kg G. lucidum and CQ. Treatment with CQ, however, produced significant reduction in hepatic TC and LDL-C compared with the extract. A dose-dependent significant increase in serum high-density lipoprotein cholesterol (HDL-C was observed in the G. lucidum treated mice compared with normal control but significantly lower compared with CQ-treated mice. Liver HDL-C level was significantly higher in CQ-treated mice compared with normal control and significantly lower compared with G. lucidum-treated and infected untreated mice. A dose-dependent effect of the extract was observed in both serum and liver very-low density lipoprotein cholesterol (VLDL-C. The implication of these results is discussed with respect to the parasite survival and proliferation in the serum and liver.

  17. Rate of red blood cell destruction varies in different strains of mice infected with Plasmodium berghei-ANKA after chronic exposure

    Directory of Open Access Journals (Sweden)

    Kikuchi Mihoko

    2009-05-01

    Full Text Available Abstract Background Severe malaria anaemia in the semi-immune individuals in the holo-endemic area has been observed to occur at low parasite density with individual variation in the responses. Thus the following has been thought to be involved: auto-immune-mediated mechanisms of uninfected red blood cell destruction, and host genetic factors to explain the differences in individual responses under the same malaria transmission. In this study, the extent of red blood cell (RBC destruction in different strains of semi-immune mice model at relatively low parasitaemia was studied. Methodology To generate semi-immunity, four strains of mice were taken through several cycles of infection and treatment. By means of immunofluorescent assay and ELISA, sera were screened for anti-erythrocyte auto-antibodies, and their relationship with haematological parameters and parasitaemia in the strains of semi-immune mice was investigated. Results Upon challenge with Plasmodium berghei ANKA after generating semi-immune status, different mean percentage haemoglobin (Hb drop was observed in the mice strains (Balb/c = 47.1%; NZW = 30.05%; C57BL/6 = 28.44%; CBA = 25.1%, which occurred on different days for each strain (for Balb/c, mean period = 13.6 days; for C57BL/6, NZW, and CBA mean period = 10.6, 10.8, 10.9 days respectively. Binding of antibody to white ghost RBCs was observed in sera of the four strains of semi-immune mice by immunofluorescence. Mean percentage Hb drop per parasitaemia was highest in Balb/c (73.6, followed by C57BL/6 (8.6, CBA (6.9 and NZW (4.0, p = 0.0005. Consequently, auto-antibodies level to ghost RBC were correlated with degree of anaemia and were highest in Balb/c, when compared with the other strains, p Conclusion The results presented in this study seem to indicate that anti-RBC auto-antibodies may be involved in the destruction of uninfected RBC in semi-immune mice at relatively low parasite burden. Host genetic factors may also

  18. Sero-epidemiological evaluation of Plasmodium falciparum malaria in Senegal.

    Science.gov (United States)

    Sylla, Khadime; Tine, Roger Clément Kouly; Ndiaye, Magatte; Sow, Doudou; Sarr, Aïssatou; Mbuyi, Marie Louise Tshibola; Diouf, Ibrahima; Lô, Amy Colé; Abiola, Annie; Seck, Mame Cheikh; Ndiaye, Mouhamadou; Badiane, Aïda Sadikh; N'Diaye, Jean Louis A; Ndiaye, Daouda; Faye, Oumar; Dieng, Thérèse; Dieng, Yémou; Ndir, Oumar; Gaye, Oumar; Faye, Babacar

    2015-07-16

    In Senegal, a significant decrease of malaria transmission intensity has been noted the last years. Parasitaemia has become lower and, therefore, more difficult to detect by microscopy. In the context of submicroscopic parasitaemia, it has become relevant to rely on relevant malaria surveillance tools to better document malaria epidemiology in such settings. Serological markers have been proposed as an essential tool for malaria surveillance. This study aimed to evaluate the sero-epidemiological situation of Plasmodium falciparum malaria in two sentinel sites in Senegal. Cross-sectional surveys were carried out in Velingara (south Senegal) and Keur Soce (central Senegal) between September and October 2010. Children under 10 years old, living in these areas, were enrolled using two-level, random sampling methods. P. falciparum infection was diagnosed using microscopy. P. falciparum antibodies against circumsporozoite protein (CSP), apical membrane protein (AMA1) and merozoite surface protein 1_42 (MSP1_42) were measured by ELISA method. A stepwise logistic regression analysis was done to assess factors associated with P. falciparum antibodies carriage. A total of 1,865 children under 10 years old were enrolled. The overall falciparum malaria prevalence was 4.99% with high prevalence in Velingara of 10.03% compared to Keur Soce of 0.3%. Symptomatic malaria cases (fever associated with parasitaemia) represented 17.37%. Seroprevalence of anti-AMA1, anti-MSP1_42 and anti-CSP antibody was 38.12, 41.55 and 40.38%, respectively. The seroprevalence was more important in Velingara and increased with age, active malaria infection and area of residence. The use of serological markers can contribute to improved malaria surveillance in areas with declining malaria transmission. This study provided useful baseline information about the sero-epidemiological situation of malaria in Senegal and can contribute to the identification of malaria hot spots in order to concentrate

  19. Backward bifurcation and optimal control of Plasmodium Knowlesi malaria

    Science.gov (United States)

    Abdullahi, Mohammed Baba; Hasan, Yahya Abu; Abdullah, Farah Aini

    2014-07-01

    A deterministic model for the transmission dynamics of Plasmodium Knowlesi malaria with direct transmission is developed. The model is analyzed using dynamical system techniques and it shows that the backward bifurcation occurs for some range of parameters. The model is extended to assess the impact of time dependent preventive (biological and chemical control) against the mosquitoes and vaccination for susceptible humans, while treatment for infected humans. The existence of optimal control is established analytically by the use of optimal control theory. Numerical simulations of the problem, suggest that applying the four control measure can effectively reduce if not eliminate the spread of Plasmodium Knowlesi in a community.

  20. Vaccination with Altered Peptide Ligands of a Plasmodium berghei Circumsporozoite Protein CD8 T-Cell Epitope: A Model to Generate T Cells Resistant to Immune Interference by Polymorphic Epitopes

    Science.gov (United States)

    Minigo, Gabriela; Flanagan, Katie L.; Slattery, Robyn M.; Plebanski, Magdalena

    2017-01-01

    Many pathogens, including the malaria parasite Plasmodium falciparum, display high levels of polymorphism within T-cell epitope regions of proteins associated with protective immunity. The T-cell epitope variants are often non-cross-reactive. Herein, we show in a murine model, which modifies a protective CD8 T-cell epitope from the circumsporozoite protein (CS) of Plasmodium berghei (SYIPSAEKI), that simultaneous or sequential co-stimulation with two of its putative similarly non-cross-reactive altered peptide ligand (APL) epitopes (SYIPSAEDI or SYIPSAEAI) has radically different effects on immunity. Hence, co-immunization or sequential stimulation in vivo of SYIPSAEKI with its APL antagonist SYIPSAEDI decreases immunity to both epitopes. By contrast, co-immunization with SYIPSAEAI has no apparent initial effect, but it renders the immune response to SYIPSAEKI resistant to being turned off by subsequent immunization with SYIPSAEDI. These results suggest a novel strategy for vaccines that target polymorphic epitopes potentially capable of mutual immune interference in the field, by initiating an immune response by co-immunization with the desired index epitope, together with a carefully selected “potentiator” APL peptide.

  1. Protection of athymic (Nu/Nu BALB/c mice against Plasmodium berghei by splenocytes from normal (Nu/ + BALB/c mice

    Directory of Open Access Journals (Sweden)

    José J. Ferraroni

    1985-12-01

    Full Text Available Athymic BALB/c (Nu/Nu mice died at 7-13 days after inoculation (DAI of Plasmodium berghei NK65, whereas their heterozygous (Nu/+ littermates died at 7-8 DAI. Nude (Nu/Nu mice, reconstituted with 2 x 10(7 splenocytes from uninfected heterozygous (Nu/+ littermates at 20 days before parasite inoculation (DBI, died about 2 days earlier than control nude mice; nude mice reconstituted at 10 or 2 DBI lived 2 to 4 days longer than control nudes; and nude mice reconstituted 2 DAI lived even longer and some survived. These findings indicate that P. berghei NK65 induces at least two T-cell dependent immune phenomena, one suppressive and the other stimulatory. Reconstitution of nude mice with T-cells from BALB/c (Nu/+ mice appeared to reduce or bypass suppressive T-cell activities which allowed the formation of a protective immune response by some of the nude mice.

  2. Late relapse of imported Plasmodium ovale malaria: a case report.

    Science.gov (United States)

    Siala, Emna; Gastli, Mondher; Essid, Rym; Jemal, Sana; Ben Abdallah, Rym; Ben Abda, Imène; Aoun, Karim; Bouratbine, Aida

    2015-06-01

    We report the first case of an imported Plasmodium ovale relapse in a Tunisian man who developed malaria three years after leaving sub- Saharan Africa. A 29-year-old Tunisian man consulted in September 2011 because of a fever, myalgia, and headache that had begun eight days earlier and persisted despite treatment with oral antibiotics. On questioning, the patient stated that he had resided three years ago for six months in Ivory Coast, where he acquired malaria. He was treated with artemether-lumefantrine. The patient said he had no recent travel to any other malaria-endemic area and had not received a blood transfusion. A first microscopy of peripheral blood smears was negative for malaria parasites. The diagnosis was established 17 days after onset of symptoms. A repeat microscopic examination of blood smears confirmed the presence of Plasmodium ovale with a parasitemia lower than 0.1%. The patient was treated with artemether lumefantrine, followed by primaquine. This case emphasizes the possibility of relapse of some plasmodial species. It highlights the importance of repeating microscopic examination of blood when the diagnosis of malaria is suspected.

  3. Development of a transgenic Plasmodium berghei line (Pb pfpkg expressing the P. falciparum cGMP-dependent protein kinase, a novel antimalarial drug target.

    Directory of Open Access Journals (Sweden)

    Rita Tewari

    Full Text Available With the inevitable selection of resistance to antimalarial drugs in treated populations, there is a need for new medicines to enter the clinic and new targets to progress through the drug discovery pipeline. In this study we set out to develop a transgenic rodent model for testing inhibitors of the Plasmodium falciparum cyclic GMP-dependent kinase in vivo. A model was needed that would allow us to investigate whether differences in amino acid sequence of this enzyme between species influences in vivo efficacy. Here we report the successful development of a transgenic P. berghei line in which the cyclic GMP-dependent protein kinase (PKG was replaced by the P. falciparum orthologue. We demonstrate that the P. falciparum orthologue was able to functionally complement the endogenous P. berghei pkg gene throughout blood stage development and early sexual development. However, subsequent development in the mosquito was severely compromised. We show that this is due to a defect in the female lineage of the transgenic by using genetic crosses with both male and female deficient P. berghei lines. This defect could be due to expression of a female-specific target in the mosquito stages of P. berghei that cannot be phosphorylated by the P. falciparum kinase. Using a previously reported anti-coccidial inhibitor of the cyclic GMP-dependent protein kinase, we show no difference in in vivo efficacy between the transgenic and control P. berghei lines. This in vivo model will be useful for screening future generations of cyclic GMP-dependent protein kinase inhibitors and allowing us to overcome any species-specific differences in the enzyme primary sequence that would influence in vivo efficacy in the rodent model. The approach will also be applicable to in vivo testing of other antimalarial compounds where the target is known.

  4. Development of a transgenic Plasmodium berghei line (Pb pfpkg) expressing the P. falciparum cGMP-dependent protein kinase, a novel antimalarial drug target.

    Science.gov (United States)

    Tewari, Rita; Patzewitz, Eva-Maria; Poulin, Benoit; Stewart, Lindsay; Baker, David A

    2014-01-01

    With the inevitable selection of resistance to antimalarial drugs in treated populations, there is a need for new medicines to enter the clinic and new targets to progress through the drug discovery pipeline. In this study we set out to develop a transgenic rodent model for testing inhibitors of the Plasmodium falciparum cyclic GMP-dependent kinase in vivo. A model was needed that would allow us to investigate whether differences in amino acid sequence of this enzyme between species influences in vivo efficacy. Here we report the successful development of a transgenic P. berghei line in which the cyclic GMP-dependent protein kinase (PKG) was replaced by the P. falciparum orthologue. We demonstrate that the P. falciparum orthologue was able to functionally complement the endogenous P. berghei pkg gene throughout blood stage development and early sexual development. However, subsequent development in the mosquito was severely compromised. We show that this is due to a defect in the female lineage of the transgenic by using genetic crosses with both male and female deficient P. berghei lines. This defect could be due to expression of a female-specific target in the mosquito stages of P. berghei that cannot be phosphorylated by the P. falciparum kinase. Using a previously reported anti-coccidial inhibitor of the cyclic GMP-dependent protein kinase, we show no difference in in vivo efficacy between the transgenic and control P. berghei lines. This in vivo model will be useful for screening future generations of cyclic GMP-dependent protein kinase inhibitors and allowing us to overcome any species-specific differences in the enzyme primary sequence that would influence in vivo efficacy in the rodent model. The approach will also be applicable to in vivo testing of other antimalarial compounds where the target is known.

  5. The Plasmodium bottleneck: malaria parasite losses in the mosquito vector

    Science.gov (United States)

    Smith, Ryan C; Vega-Rodríguez, Joel; Jacobs-Lorena, Marcelo

    2014-01-01

    Nearly one million people are killed every year by the malaria parasite Plasmodium. Although the disease-causing forms of the parasite exist only in the human blood, mosquitoes of the genus Anopheles are the obligate vector for transmission. Here, we review the parasite life cycle in the vector and highlight the human and mosquito contributions that limit malaria parasite development in the mosquito host. We address parasite killing in its mosquito host and bottlenecks in parasite numbers that might guide intervention strategies to prevent transmission. PMID:25185005

  6. The Plasmodium bottleneck: malaria parasite losses in the mosquito vector

    Directory of Open Access Journals (Sweden)

    Ryan C Smith

    2014-08-01

    Full Text Available Nearly one million people are killed every year by the malaria parasite Plasmodium. Although the disease-causing forms of the parasite exist only in the human blood, mosquitoes of the genus Anopheles are the obligate vector for transmission. Here, we review the parasite life cycle in the vector and highlight the human and mosquito contributions that limit malaria parasite development in the mosquito host. We address parasite killing in its mosquito host and bottlenecks in parasite numbers that might guide intervention strategies to prevent transmission.

  7. Transcriptomic evidence for modulation of host inflammatory responses during febrile Plasmodium falciparum malaria

    NARCIS (Netherlands)

    Tran, T.M.; Jones, M.B.; Ongoiba, A.; Bijker, E.M.; Schats, R.; Venepally, P.; Skinner, J.; Doumbo, S.; Quinten, E.; Visser, L.G.; Whalen, E.; Presnell, S.; O'Connell, E.M.; Kayentao, K.; Doumbo, O.K.; Chaussabel, D.; Lorenzi, H.; Nutman, T.B.; Ottenhoff, T.H.; Haks, M.C.; Traore, B.; Kirkness, E.F.; Sauerwein, R.W.; Crompton, P.D.

    2016-01-01

    Identifying molecular predictors and mechanisms of malaria disease is important for understanding how Plasmodium falciparum malaria is controlled. Transcriptomic studies in humans have so far been limited to retrospective analysis of blood samples from clinical cases. In this prospective,

  8. 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.

  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. Parasite virulence and disease severity in Plasmodium falciparum malaria.

    OpenAIRE

    Ribacke, Ulf

    2009-01-01

    Malaria stands out as one of the most important infectious diseases and one of the world s leading causes of death. Plasmodium falciparum is the parasite responsible for the great majority of severe disease syndromes and mortality, and affects mainly children and pregnant women. Despite intensive research efforts, the understanding of P. falciparum virulence is limited. Infections with the parasite cause everything from asymptomatic parasitemia to severe disease and death, a...

  11. CRISPR-mediated genome editing of Plasmodium falciparum malaria parasites.

    Science.gov (United States)

    Lee, Marcus Cs; Fidock, David A

    2014-01-01

    The development of the CRISPR-Cas system is revolutionizing genome editing in a variety of organisms. The system has now been used to manipulate the genome of Plasmodium falciparum, the most lethal malaria-causing species. The ability to generate gene deletions or nucleotide substitutions rapidly and economically promises to accelerate the analysis of novel drug targets and to help elucidate the function of specific genes or gene families, while complementing genome-wide association studies.

  12. CRISPR-mediated genome editing of Plasmodium falciparum malaria parasites

    OpenAIRE

    Lee, Marcus CS; David A Fidock

    2014-01-01

    The development of the CRISPR-Cas system is revolutionizing genome editing in a variety of organisms. The system has now been used to manipulate the genome of Plasmodium falciparum, the most lethal malaria-causing species. The ability to generate gene deletions or nucleotide substitutions rapidly and economically promises to accelerate the analysis of novel drug targets and to help elucidate the function of specific genes or gene families, while complementing genome-wide association studies.

  13. Artesunate plus pyronaridine for treating uncomplicated Plasmodium falciparum malaria

    OpenAIRE

    Bukirwa, Hasifa; Unnikrishnan, B; Kramer, Christine V; Sinclair, David; Nair, Suma; Tharyan, Prathap

    2014-01-01

    Background The World Health Organization (WHO) recommends that people with uncomplicated Plasmodium falciparum malaria are treated using Artemisinin-based Combination Therapy (ACT). ACT combines three-days of a short-acting artemisinin derivative with a longer-acting antimalarial which has a different mode of action. Pyronaridine has been reported as an effective antimalarial over two decades of use in parts of Asia, and is currently being evaluated as a partner drug for artesunate. Objective...

  14. 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.

  15. 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.

  16. Plasmodium malariae and Plasmodium ovale infections in the China-Myanmar border area.

    Science.gov (United States)

    Li, Peipei; Zhao, Zhenjun; Xing, Hua; Li, Wenli; Zhu, Xiaotong; Cao, Yaming; Yang, Zhaoqing; Sattabongkot, Jetsumon; Yan, Guiyun; Fan, Qi; Cui, Liwang

    2016-11-15

    The Greater Mekong Subregion is aiming to achieve regional malaria elimination by 2030. Though a shift in malaria parasite species predominance by Plasmodium vivax has been recently documented, the transmission of the two minor Plasmodium species, Plasmodium malariae and Plasmodium ovale spp., is poorly characterized in the region. This study aims to determine the prevalence of these minor species in the China-Myanmar border area and their genetic diversity. Epidemiology study was conducted during passive case detection in hospitals and clinics in Myanmar and four counties in China along the China-Myanmar border. Cross-sectional surveys were conducted in villages and camps for internally displaced persons to determine the prevalence of malaria infections. Malaria infections were diagnosed initially by microscopy and later in the laboratory using nested PCR for the SSU rRNA genes. Plasmodium malariae and P. ovale infections were confirmed by sequencing the PCR products. The P. ovale subtypes were determined by sequencing the Pocytb, Pocox1 and Pog3p genes. Parasite populations were evaluated by PCR amplification and sequencing of the MSP-1 genes. Antifolate sensitivity was assessed by sequencing the dhfr-ts and dhps genes from the P. malariae and P. ovale isolates. Analysis of 2701 blood samples collected from the China-Myanmar border by nested PCR targeting the parasite SSU rRNA genes identified 561 malaria cases, including 161 Plasmodium falciparum, 327 P. vivax, 66 P. falciparum/P. vivax mixed infections, 4 P. malariae and 3 P. ovale spp. P. vivax and P. falciparum accounted for >60 and ~30% of all malaria cases, respectively. In comparison, the prevalence of P. malariae and P. ovale spp. was very low and only made up ~1% of all PCR-positive cases. Nevertheless, these two species were often misidentified as P. vivax infections or completely missed by microscopy even among symptomatic patients. Phylogenetic analysis of the SSU rRNA, Pocytb, Pocox1 and Pog3p genes

  17. The prognostic value of schizontaemia in imported Plasmodium falciparum malaria

    Science.gov (United States)

    2012-01-01

    Background In Plasmodium falciparum infection, peripheral parasite counts do not always correlate well with the sequestered parasite burden. As erythrocytes parasitized with mature trophozoites and schizonts have a high tendency to adhere to the microvascular endothelium, they are often absent in peripheral blood samples. The appearance of schizonts in peripheral blood smears is thought to be a marker of high sequestered parasite burden and severe disease. In the present study, the value of schizontaemia as an early marker for severe disease in non-immune individuals with imported malaria was evaluated. Methods All patients in the Rotterdam Malaria Cohort diagnosed with P. falciparum malaria between 1 January 1999 and 1 January 2012 were included. Thick and thin blood films were examined for the presence of schizontaemia. The occurrence of WHO defined severe malaria was the primary endpoint. The diagnostic performance of schizontaemia was compared with previously evaluated biomarkers C-reactive protein and lactate. Results Schizonts were present on admission in 49 of 401 (12.2%) patients. Patients with schizontaemia were more likely to present with severe malaria, a more complicated course and had longer duration of admission in hospital. Schizontaemia had a specificity of 0.95, a sensitivity of 0.53, a negative predictive value of 0.92 and a positive predictive value of 0.67 for severe malaria. The presence of schizonts was an independent predictor for severe malaria. Conclusion Absence of schizonts was found to be a specific marker for exclusion of severe malaria. Presence of schizonts on admission was associated with a high positive predictive value for severe malaria. This may be of help to identify patients who are at risk of a more severe course than would be expected when considering peripheral parasitaemia alone. PMID:22929647

  18. Complement activation in Ghanaian children with severe Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Helegbe, Gideon K; Goka, Bamenla Q; Kurtzhals, Jørgen

    2007-01-01

    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......55)] 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...... 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...

  19. BIOLOGY OF HUMAN MALARIA PLASMODIA INCLUDING PLASMODIUM KNOWLESI

    Directory of Open Access Journals (Sweden)

    Spinello Antinori

    2012-03-01

    Full Text Available Malaria is a vector-borne infection caused by unicellular parasite of the genus Plasmodium. Plasmodia are obligate intracellular parasites that in humans after a clinically silent replication phase in the liver are able to infect and replicate within the erythrocytes. Four species (P.falciparum, P.malariae, P.ovale and P.vivax are traditionally recognized as responsible of natural infection in human beings but the recent upsurge of P.knowlesi malaria in South-East Asia has led clinicians to consider it as the fifth human malaria parasite. Recent studies in wild-living apes in Africa have revealed that P.falciparum, the most deadly form of human malaria, is not only human-host restricted as previously believed and its phylogenetic lineage is much more complex with new species identified in gorilla, bonobo and chimpanzee. Although less impressive, new data on biology of P.malariae, P.ovale and P.vivax are also emerging and will be briefly discussed in this review.

  20. 遗传减毒伯氏疟原虫ANKA株的构建及其免疫保护效应%Establishment of a genetically attenuated strain of Plasmodium berghei ANKA and its immune protective effect

    Institute of Scientific and Technical Information of China (English)

    丁艳; 谭章平; 卢潇; 徐文岳; 付雍

    2016-01-01

    recombinant parasites were then performed. At last, C57BL/6J mice were immunized with the attenuated parasite and challenged subsequently for observation of immune protective effect. Results We successfully amplified 3 independent fragment 5′UTR, 3′hDHFR and UTR, and the length were 798, 1 628 and 759 bp, respectively. After fusion PCR reaction, full-length recombinant fragment 5′UTR+hDHFR+3′UTR was constructed, and the length was 3 185 bp. Genetically attenuated strain of Plasmodium berghei ANKA was generated by introducing the full-length recombinant 5′UTR+hDHFR+3′UTR fragment into schizonts. Then mice were immunized with this genetic attenuated strain and challenged by wild type of Plasmodium berghei ANKA subsequently. The parasitemia of immunized mice was 0%; experimental cerebral malaria incidence was 0% and survival rate was 100%. Mice acquired antimalarial immunity after vaccination with genetically attenuated parasites. Conclusion Genetically attenuated strain of Plasmodium berghei ANKA was successfully established and could arouse complete protection to mice against malaria infection. This work could provide insights into the mechanisms of protective immunity induced by pre-erythrocytic malaria vaccine.

  1. Comparative population structure of Plasmodium malariae and Plasmodium falciparum under different transmission settings in Malawi

    Directory of Open Access Journals (Sweden)

    Molyneux Malcolm E

    2011-02-01

    Full Text Available Abstract Background Described here is the first population genetic study of Plasmodium malariae, the causative agent of quartan malaria. Although not as deadly as Plasmodium falciparum, P. malariae is more common than previously thought, and is frequently in sympatry and co-infection with P. falciparum, making its study increasingly important. This study compares the population parameters of the two species in two districts of Malawi with different malaria transmission patterns - one seasonal, one perennial - to explore the effects of transmission on population structures. Methods Six species-specific microsatellite markers were used to analyse 257 P. malariae samples and 257 P. falciparum samples matched for age, gender and village of residence. Allele sizes were scored to within 2 bp for each locus and haplotypes were constructed from dominant alleles in multiple infections. Analysis of multiplicity of infection (MOI, population differentiation, clustering of haplotypes and linkage disequilibrium was performed for both species. Regression analyses were used to determine association of MOI measurements with clinical malaria parameters. Results Multiple-genotype infections within each species were common in both districts, accounting for 86.0% of P. falciparum and 73.2% of P. malariae infections and did not differ significantly with transmission setting. Mean MOI of P. falciparum was increased under perennial transmission compared with seasonal (3.14 vs 2.59, p = 0.008 and was greater in children compared with adults. In contrast, P. malariae mean MOI was similar between transmission settings (2.12 vs 2.11 and there was no difference between children and adults. Population differentiation showed no significant differences between villages or districts for either species. There was no evidence of geographical clustering of haplotypes. Linkage disequilibrium amongst loci was found only for P. falciparum samples from the seasonal transmission

  2. 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.

  3. Interactive transcriptome analysis of malaria patients and infecting Plasmodium falciparum.

    Science.gov (United States)

    Yamagishi, Junya; Natori, Anna; Tolba, Mohammed E M; Mongan, Arthur E; Sugimoto, Chihiro; Katayama, Toshiaki; Kawashima, Shuichi; Makalowski, Wojciech; Maeda, Ryuichiro; Eshita, Yuki; Tuda, Josef; Suzuki, Yutaka

    2014-09-01

    To understand the molecular mechanisms of parasitism in vivo, it is essential to elucidate how the transcriptomes of the human hosts and the infecting parasites affect one another. Here we report the RNA-seq analysis of 116 Indonesian patients infected with the malaria parasite Plasmodium falciparum (Pf). We extracted RNAs from their peripheral blood as a mixture of host and parasite transcripts and mapped the RNA-seq tags to the human and Pf reference genomes to separate the respective tags. We were thus able to simultaneously analyze expression patterns in both humans and parasites. We identified human and parasite genes and pathways that correlated with various clinical data, which may serve as primary targets for drug developments. Of particular importance, we revealed characteristic expression changes in the human innate immune response pathway genes including TLR2 and TICAM2 that correlated with the severity of the malaria infection. We also found a group of transcription regulatory factors, JUND, for example, and signaling molecules, TNFAIP3, for example, that were strongly correlated in the expression patterns of humans and parasites. We also identified several genetic variations in important anti-malaria drug resistance-related genes. Furthermore, we identified the genetic variations which are potentially associated with severe malaria symptoms both in humans and parasites. The newly generated data should collectively lay a unique foundation for understanding variable behaviors of the field malaria parasites, which are far more complex than those observed under laboratory conditions.

  4. Two cases of Plasmodium falciparum malaria in the Netherlands without recent travel to a malaria-endemic country.

    Science.gov (United States)

    Arends, Joop E; Oosterheert, Jan Jelrik; Kraaij-Dirkzwager, Marleen M; Kaan, Jan A; Fanoy, Ewout B; Haas, Pieter-Jan; Scholte, Ernst-Jan; Kortbeek, Laetitia M; Sankatsing, Sanjay U C

    2013-09-01

    Recently, two patients of African origin were given a diagnosis of Plasmodium falciparum malaria without recent travel to a malaria-endemic country. This observation highlights the importance for clinicians to consider tropical malaria in patients with fever. Possible transmission routes of P. falciparum to these patients will be discussed. From a public health perspective, international collaboration is crucial when potential cases of European autochthonous P. falciparum malaria in Europe re considered.

  5. Major Histocompatibility Complex and Malaria: Focus on Plasmodium vivax infection

    Directory of Open Access Journals (Sweden)

    Josué Costa Lima-Junior

    2016-01-01

    Full Text Available The importance of host and parasite genetic factors in malaria resistance or susceptibility has been investigated since the middle of the last century. Nowadays, of all diseases that affect man, malaria still plays one of the highest levels of selective pressure on human genome. Susceptibility to malaria depends on exposure profile, epidemiological characteristics and several components of the innate and adaptive immune system that influences the quality of the immune response generated during the Plasmodium lifecycle in the vertebrate host. But it is well known that the parasite’s enormous capacity of genetic variation in conjunction with the host genetics polymorphism is also associated with a wide spectrum of susceptibility degrees to complicated or severe forms of the disease. In this scenario, variations in genes of the Major Histocompatibility Complex (MHC associated with host resistance or susceptibility to malaria, have been identified and used as markers in host-pathogen interaction studies, mainly those evaluating the impact on the immune response, acquisition of resistance or increased susceptibility to infection or vulnerability to disease. However, due to the intense selective pressure, number of cases and mortality rates, the majority of the reported associations reported concerned Plasmodium falciparum malaria. Studies on the MHC polymorphism and its association with P. vivax, which is the most widespread Plasmodium and the most prevalent species outside the African continent, are less frequent but equally important. Despite punctual contributions, there are accumulated evidences of human genetic control in P. vivax infection and disease. Herein we review the current knowledge in the field of MHC and derived molecules (HLA Class I, Class II, TNF-α, LTA, BAT1 and CTL4 regarding P. vivax malaria. We discuss particularly the results of P. vivax studies on HLA class I and II polymorphisms in relation to host susceptibility

  6. Antiplasmodial activity of certain medicinal plants against chloroquine resistant Plasmodium berghei infected white albino BALB/c mice.

    Science.gov (United States)

    Rajendran, C; Begam, M; Kumar, Dharmendra; Baruah, Indra; Gogoi, H K; Srivastava, R B; Veer, Vijay

    2014-06-01

    In the present study of antimalarial efficacy, aqueous extracts of leaves and unripe fruits of Psidium guajava, leaves of Ocimum sanctum and leaves of Murraya koenigii are evaluated against Plasmodium berghei (chloroquine resistant NK65 strain) infected white albino BALB/c mice. A 7 days oral administration was adopted with different dosage viz., 350 mg, 750 mg and 1,000 mg/kg body weight as treatment schedule along with parasite (Group I) and drug control with Chloroquine, 50 mg/kg body weight (Group II). All the parts were extracted based on the decoction method, which is commonly seen among the villagers/tribes as their usual method of preparation of decoction for most of the ailments. The antimalarial activities were evaluated from the giemsa stained blood smears collected from different treated groups of mice used in this experiment. The antiplasmodial effect that is percent parasitaemia and percent suppression (values in parenthesis) showed by the treated groups of mice at 350 mg/kg b. wt. by the aqueous extracts of P. guajava leaves (Group III) was 19.8 ± 1.22 (73.7 %), P. guajava unripe fruits (Group IV) was 52.7 ± 2.19 (30.0 %), leaves of O. sanctum (Group V) was 64.0 ± 0.73 (15.1 %) and leaves of M. koenigii (Group VI) was 28.9 ± 0.81 (61.6 %) whereas at 750 mg/kg b. wt., it all showed 10.3 ± 0.7 (80.2 %), 26.3 ± 0.52 (65.1 %), 42.0 ± 0.47 (44.2 %) and 14.9 ± 0.46 (71.5 %) whereas at 1,000 mg/kg b. wt. dose, it all showed 9.2 ± 0.39 (85.8 %), 25.6 ± 0.40 (62.0 %), 41.8 ± 0.29 (35.5 %) and 14.0 ± 0.42 (76.9 %) respectively.

  7. Modelling the incidence of Plasmodium vivax and Plasmodium falciparum malaria in Afghanistan 2006-2009.

    Science.gov (United States)

    Alegana, Victor A; Wright, Jim A; Nahzat, Sami M; Butt, Waqar; Sediqi, Amad W; Habib, Naeem; Snow, Robert W; Atkinson, Peter M; Noor, Abdisalan M

    2014-01-01

    Identifying areas that support high malaria risks and where populations lack access to health care is central to reducing the burden in Afghanistan. This study investigated the incidence of Plasmodium vivax and Plasmodium falciparum using routine data to help focus malaria interventions. To estimate incidence, the study modelled utilisation of the public health sector using fever treatment data from the 2012 national Malaria Indicator Survey. A probabilistic measure of attendance was applied to population density metrics to define the proportion of the population within catchment of a public health facility. Malaria data were used in a Bayesian spatio-temporal conditional-autoregressive model with ecological or environmental covariates, to examine the spatial and temporal variation of incidence. From the analysis of healthcare utilisation, over 80% of the population was within 2 hours' travel of the nearest public health facility, while 64.4% were within 30 minutes' travel. The mean incidence of P. vivax in 2009 was 5.4 (95% Crl 3.2-9.2) cases per 1000 population compared to 1.2 (95% Crl 0.4-2.9) cases per 1000 population for P. falciparum. P. vivax peaked in August while P. falciparum peaked in November. 32% of the estimated 30.5 million people lived in regions where annual incidence was at least 1 case per 1,000 population of P. vivax; 23.7% of the population lived in areas where annual P. falciparum case incidence was at least 1 per 1000. This study showed how routine data can be combined with household survey data to model malaria incidence. The incidence of both P. vivax and P. falciparum in Afghanistan remain low but the co-distribution of both parasites and the lag in their peak season provides challenges to malaria control in Afghanistan. Future improved case definition to determine levels of imported risks may be useful for the elimination ambitions in Afghanistan.

  8. Malaria risk factor assessment using active and passive surveillance data from Aceh Besar, Indonesia, a low endemic, malaria elimination setting with Plasmodium knowlesi, Plasmodium vivax, and Plasmodium falciparum.

    Science.gov (United States)

    Herdiana, Herdiana; Cotter, Chris; Coutrier, Farah N; Zarlinda, Iska; Zelman, Brittany W; Tirta, Yusrifar Kharisma; Greenhouse, Bryan; Gosling, Roly D; Baker, Peter; Whittaker, Maxine; Hsiang, Michelle S

    2016-09-13

    As malaria transmission declines, it becomes more geographically focused and more likely due to asymptomatic and non-falciparum infections. To inform malaria elimination planning in the context of this changing epidemiology, local assessments on the risk factors for malaria infection are necessary, yet challenging due to the low number of malaria cases. A population-based, cross-sectional study was performed using passive and active surveillance data collected in Aceh Besar District, Indonesia from 2014 to 2015. Malaria infection was defined as symptomatic polymerase chain reaction (PCR)-confirmed infection in index cases reported from health facilities, and asymptomatic or symptomatic PCR-confirmed infection identified in reactive case detection (RACD). Potential risk factors for any infection, species-specific infection, or secondary-case detection in RACD were assessed through questionnaires and evaluated for associations. Nineteen Plasmodium knowlesi, 12 Plasmodium vivax and six Plasmodium falciparum cases were identified passively, and 1495 community members screened in RACD, of which six secondary cases were detected (one P. knowlesi, three P. vivax, and two P. falciparum, with four being asymptomatic). Compared to non-infected subjects screened in RACD, cases identified through passive or active surveillance were more likely to be male (AOR 12.5, 95 % CI 3.0-52.1), adult (AOR 14.0, 95 % CI 2.2-89.6 for age 16-45 years compared to malaria infection in index and RACD identified cases was associated with forest exposure, particularly overnights in the forest for work. In low-transmission settings, utilization of data available through routine passive and active surveillance can support efforts to target individuals at high risk.

  9. 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.

  10. A simple and fast method to exclude high Plasmodium falciparum parasitaemia in travellers with imported malaria

    NARCIS (Netherlands)

    T. van Gool (Tom); M.E. van Wolfswinkel (Marlies); R. Koelewijn (Rob); P.P.A.M. van Thiel (Pieter); J. Jacobs (Jan); J.J. van Hellemond (Jaap); P.J.J. van Genderen (Perry)

    2011-01-01

    textabstractBackground: Counts of malaria parasites in peripheral blood are important to assess severity of Plasmodium falciparum malaria. Thin and thick smears are routinely used for this purpose. Methods. In this study the Binax NOW® Malaria Test, an easy-to-perform rapid diagnostic test, with His

  11. A simple and fast method to exclude high Plasmodium falciparum parasitaemia in travellers with imported malaria

    NARCIS (Netherlands)

    T. van Gool (Tom); M.E. van Wolfswinkel (Marlies); R. Koelewijn (Rob); P.P.A.M. van Thiel (Pieter); J. Jacobs (Jan); J.J. van Hellemond (Jaap); P.J.J. van Genderen (Perry)

    2011-01-01

    textabstractBackground: Counts of malaria parasites in peripheral blood are important to assess severity of Plasmodium falciparum malaria. Thin and thick smears are routinely used for this purpose. Methods. In this study the Binax NOW® Malaria Test, an easy-to-perform rapid diagnostic test, with

  12. A simple and fast method to exclude high Plasmodium falciparum parasitaemia in travellers with imported malaria

    NARCIS (Netherlands)

    T. van Gool (Tom); M.E. van Wolfswinkel (Marlies); R. Koelewijn (Rob); P.P.A.M. van Thiel (Pieter); J. Jacobs (Jan); J.J. van Hellemond (Jaap); P.J.J. van Genderen (Perry)

    2011-01-01

    textabstractBackground: Counts of malaria parasites in peripheral blood are important to assess severity of Plasmodium falciparum malaria. Thin and thick smears are routinely used for this purpose. Methods. In this study the Binax NOW® Malaria Test, an easy-to-perform rapid diagnostic test, with His

  13. Human immune system mice immunized with Plasmodium falciparum circumsporozoite protein induce protective human humoral immunity against malaria.

    Science.gov (United States)

    Huang, Jing; Li, Xiangming; Coelho-dos-Reis, Jordana G A; Zhang, Min; Mitchell, Robert; Nogueira, Raquel Tayar; Tsao, Tiffany; Noe, Amy R; Ayala, Ramses; Sahi, Vincent; Gutierrez, Gabriel M; Nussenzweig, Victor; Wilson, James M; Nardin, Elizabeth H; Nussenzweig, Ruth S; Tsuji, Moriya

    2015-12-01

    In this study, we developed human immune system (HIS) mice that possess functional human CD4+ T cells and B cells, named HIS-CD4/B mice. HIS-CD4/B mice were generated by first introducing HLA class II genes, including DR1 and DR4, along with genes encoding various human cytokines and human B cell activation factor (BAFF) to NSG mice by adeno-associated virus serotype 9 (AAV9) vectors, followed by engrafting human hematopoietic stem cells (HSCs). HIS-CD4/B mice, in which the reconstitution of human CD4+ T and B cells resembles to that of humans, produced a significant level of human IgG against Plasmodium falciparum circumsporozoite (PfCS) protein upon immunization. CD4+ T cells in HIS-CD4/B mice, which possess central and effector memory phenotypes like those in humans, are functional, since PfCS protein-specific human CD4+ T cells secreting IFN-γ and IL-2 were detected in immunized HIS-CD4/B mice. Lastly, PfCS protein-immunized HIS-CD4/B mice were protected from in vivo challenge with transgenic P. berghei sporozoites expressing the PfCS protein. The immune sera collected from protected HIS-CD4/B mice reacted against transgenic P. berghei sporozoites expressing the PfCS protein and also inhibited the parasite invasion into hepatocytes in vitro. Taken together, these studies show that our HIS-CD4/B mice could mount protective human anti-malaria immunity, consisting of human IgG and human CD4+ T cell responses both specific for a human malaria antigen.

  14. Host PI(3,5)P2 activity is required for Plasmodium berghei growth during liver stage infection.

    Science.gov (United States)

    Thieleke-Matos, Carolina; da Silva, Mafalda Lopes; Cabrita-Santos, Laura; Pires, Cristiana F; Ramalho, José S; Ikonomov, Ognian; Seixas, Elsa; Shisheva, Assia; Seabra, Miguel C; Barral, Duarte C

    2014-10-01

    Malaria parasites go through an obligatory liver stage before they infect erythrocytes and cause disease symptoms. In the host hepatocytes, the parasite is enclosed by a parasitophorous vacuole membrane (PVM). Here, we dissected the interaction between the Plasmodium parasite and the host cell late endocytic pathway and show that parasite growth is dependent on the phosphoinositide 5-kinase (PIKfyve) that converts phosphatidylinositol 3-phosphate [PI(3)P] into phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2 ] in the endosomal system. We found that inhibition of PIKfyve by either pharmacological or non-pharmacological means causes a delay in parasite growth. Moreover, we show that the PI(3,5)P2 effector protein TRPML1 that is involved in late endocytic membrane fusion, is present in vesicles closely contacting the PVM and is necessary for parasite growth. Thus, our studies suggest that the parasite PVM is able to fuse with host late endocytic vesicles in a PI(3,5)P2 -dependent manner, allowing the exchange of material between the host and the parasite, which is essential for successful infection.

  15. The IFN-γ-inducible GTPase, Irga6, protects mice against Toxoplasma gondii but not against Plasmodium berghei and some other intracellular pathogens.

    Directory of Open Access Journals (Sweden)

    Oliver Liesenfeld

    Full Text Available Clearance of infection with intracellular pathogens in mice involves interferon-regulated GTPases of the IRG protein family. Experiments with mice genetically deficient in members of this family such as Irgm1(LRG-47, Irgm3(IGTP, and Irgd(IRG-47 has revealed a critical role in microbial clearance, especially for Toxoplasma gondii. The in vivo role of another member of this family, Irga6 (IIGP, IIGP1 has been studied in less detail. We investigated the susceptibility of two independently generated mouse strains deficient in Irga6 to in vivo infection with T. gondii, Mycobacterium tuberculosis, Leishmania mexicana, L. major, Listeria monocytogenes, Anaplasma phagocytophilum and Plasmodium berghei. Compared with wild-type mice, mice deficient in Irga6 showed increased susceptibility to oral and intraperitoneal infection with T. gondii but not to infection with the other organisms. Surprisingly, infection of Irga6-deficient mice with the related apicomplexan parasite, P. berghei, did not result in increased replication in the liver stage and no Irga6 (or any other IRG protein was detected at the parasitophorous vacuole membrane in IFN-γ-induced wild-type cells infected with P. berghei in vitro. Susceptibility to infection with T. gondii was associated with increased mortality and reduced time to death, increased numbers of inflammatory foci in the brains and elevated parasite loads in brains of infected Irga6-deficient mice. In vitro, Irga6-deficient macrophages and fibroblasts stimulated with IFN-γ were defective in controlling parasite replication. Taken together, our results implicate Irga6 in the control of infection with T. gondii and further highlight the importance of the IRG system for resistance to this pathogen.

  16. The IFN-γ-Inducible GTPase, Irga6, Protects Mice against Toxoplasma gondii but Not against Plasmodium berghei and Some Other Intracellular Pathogens

    Science.gov (United States)

    Han, Seong-Ji; Heinrich, Frederik; Muñoz, Melba; Kaiser, Frank; Aebischer, Toni; Buch, Thorsten; Waisman, Ari; Reichmann, Gaby; Utermöhlen, Olaf; von Stebut, Esther; von Loewenich, Friederike D.; Bogdan, Christian; Specht, Sabine; Saeftel, Michael; Hoerauf, Achim; Mota, Maria M.; Könen-Waisman, Stephanie; Kaufmann, Stefan H. E.; Howard, Jonathan C.

    2011-01-01

    Clearance of infection with intracellular pathogens in mice involves interferon-regulated GTPases of the IRG protein family. Experiments with mice genetically deficient in members of this family such as Irgm1(LRG-47), Irgm3(IGTP), and Irgd(IRG-47) has revealed a critical role in microbial clearance, especially for Toxoplasma gondii. The in vivo role of another member of this family, Irga6 (IIGP, IIGP1) has been studied in less detail. We investigated the susceptibility of two independently generated mouse strains deficient in Irga6 to in vivo infection with T. gondii, Mycobacterium tuberculosis, Leishmania mexicana, L. major, Listeria monocytogenes, Anaplasma phagocytophilum and Plasmodium berghei. Compared with wild-type mice, mice deficient in Irga6 showed increased susceptibility to oral and intraperitoneal infection with T. gondii but not to infection with the other organisms. Surprisingly, infection of Irga6-deficient mice with the related apicomplexan parasite, P. berghei, did not result in increased replication in the liver stage and no Irga6 (or any other IRG protein) was detected at the parasitophorous vacuole membrane in IFN-γ-induced wild-type cells infected with P. berghei in vitro. Susceptibility to infection with T. gondii was associated with increased mortality and reduced time to death, increased numbers of inflammatory foci in the brains and elevated parasite loads in brains of infected Irga6-deficient mice. In vitro, Irga6-deficient macrophages and fibroblasts stimulated with IFN-γ were defective in controlling parasite replication. Taken together, our results implicate Irga6 in the control of infection with T. gondii and further highlight the importance of the IRG system for resistance to this pathogen. PMID:21698150

  17. Plasmodium chabaudi chabaudi malaria parasites can develop stable resistance to atovaquone with a mutation in the cytochrome b gene

    Directory of Open Access Journals (Sweden)

    Alves Ana C

    2010-05-01

    Full Text Available Abstract Background Plasmodium falciparum, has developed resistance to many of the drugs in use. The recommended treatment policy is now to use drug combinations. The atovaquone-proguanil (AP drug combination, is one of the treatment and prophylaxis options. Atovaquone (ATQ exerts its action by inhibiting plasmodial mitochondria electron transport at the level of the cytochrome bc1 complex. Plasmodium falciparum in vitro resistance to ATQ has been associated with specific point mutations in the region spanning codons 271-284 of the cytochrome b gene. ATQ -resistant Plasmodium yoelii and Plasmodium berghei lines have been obtained and resistant lines have amino acid mutations in their CYT b protein sequences. Plasmodium chabaudi model for studying drug-responses and drug-resistance selection is a very useful rodent malaria model but no ATQ resistant parasites have been reported so far. The aim of this study was to determine the ATQ sensitivity of the P. chabaudi clones, to select a resistant parasite line and to perform genotypic characterization of the cytb gene of these clones. Methods To select for ATQ resistance, Plasmodium. chabaudi chabaudi clones were exposed to gradually increasing concentrations of ATQ during several consecutive passages in mice. Plasmodium chabaudi cytb gene was amplified and sequenced. Results ATQ resistance was selected from the clone AS-3CQ. In order to confirm whether an heritable genetic mutation underlies the response of AS-ATQ to ATQ, the stability of the drug resistance phenotype in this clone was evaluated by measuring drug responses after (i multiple blood passages in the absence of the drug, (ii freeze/thawing of parasites in liquid nitrogen and (iii transmission through a mosquito host, Anopheles stephensi. ATQ resistance phenotype of the drug-selected parasite clone kept unaltered. Therefore, ATQ resistance in clone AS-ATQ is genetically encoded. The Minimum Curative Dose of AS-ATQ showed a six

  18. The increasing importance of Plasmodium ovale and Plasmodium malariae in a malaria elimination setting: an observational study of imported cases in Jiangsu Province, China, 2011-2014.

    Science.gov (United States)

    Cao, Yuanyuan; Wang, Weiming; Liu, Yaobao; Cotter, Chris; Zhou, Huayun; Zhu, Guoding; Tang, Jianxia; Tang, Feng; Lu, Feng; Xu, Sui; Gu, Yaping; Zhang, Chao; Li, Julin; Cao, Jun

    2016-09-07

    Following initiation of China's National Malaria Elimination Action Plan in 2010, indigenous malaria infections in Jiangsu Province decreased significantly. Meanwhile imported Plasmodium infections have increased substantially, particularly Plasmodium ovale and Plasmodium malariae. Given the risk for malaria resurgence, there is an urgent need to understand the increase in imported P. ovale and P. malariae infections as China works to achieve national malaria elimination. An observational study of imported malaria cases in Jiangsu Province, China was carried out for the period of 2011-2014. A total of 1268 malaria cases were reported in Jiangsu Province from 2011 to 2014. Although imported Plasmodium falciparum cases (n = 1058) accounted for 83.4 % of all reported cases in Jiangsu, P. ovale cases (14, 19, 30, and 46) and their proportion (3.7, 9.6, 8.8, and 13.0 %) of all malaria cases increased over the 4 years. Similarly, P. malariae cases (seven, two, nine, and 10) and proportion (1.9, 1.0, 2.6, and 2.8 %) of all malaria cases increased slightly during this time. A total of 98 cases of Plasmodium ovale curtisi (47/98, 48 %) and Plasmodium ovale wallikeri (51/98, 52 %) were identified as well. Latency periods were significant among these Plasmodium infections (p = 0.00). Also, this study found that the latency periods of P. ovale sp., P. malariae and Plasmodium vivax were significantly longer than P. falciparum. However, for both P. ovale curtisi and P. ovale wallikeri infections, the latency period analysis was not significant (p = 0.81). Misdiagnosis of both P. ovale and P. malariae was greater than 71.5 and 71.4 %, respectively. The P. ovale cases were misdiagnosed as P. falciparum (35 cases, 32.1 %), P. vivax (43 cases, 39.4 %) by lower levels of CDCs or hospitals. And, the P. malariae cases were misdiagnosed as P. falciparum (ten cases, 35.7 %), P. vivax (nine cases, 32.1 %) and P. ovale sp. (one case, 3.6 %). Geographic distribution of

  19. Changing trends in prevalence of different Plasmodium species with dominance of Plasmodium falciparum malaria infection in Aligarh (India).

    Science.gov (United States)

    Khan, Haris M; Shujatullah, Fatima; Ashfaq, Mohammad; Raza, Adil

    2011-01-01

    To determine the prevalence of malaria in Aligarh and analyze species dominance in different years over a decade. Diagnosis of malaria was done using microscopy as gold standard, rapid antigen detection assays and quantitative buffy coat (QBC) assays. Giemsa stained blood smear examination was done, thick and thin films were examined for presence of different Plasmodium spp. Rapid antigen detection assays employing detection of HRP-2 and parasite lactate dehydrogenase antigen (pLDH) by immunochromatography was done in patients whose blood smear found to be negative by conventional Giemsa slide examination. QBC was done in cases where there is strong clinical suspicion of malaria with blood smear negative, in patients with chronic malaria, splenomegaly, or in those patients who had inadequate treatment and for post-treatment follow up. Plasmodium vivax and Plasmodium falciparum were only species detected in our hospital. Overall prevalence of malaria in Aligarh was found to be 8.8%. The maximum prevalence of 20.1% was observed in year 2008 and lowest 2.3% in 2002. High prevalence of malaria is observed in this part of country with dominance of both species particularly Plasmodium falciparum should be monitored and factors accounting for occurrence should be studied to employ effective control measures. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  20. Changing trends in prevalence of different Plasmodium species with dominance of Plasmodium falciparum malaria infection in Aligarh (India)

    Institute of Scientific and Technical Information of China (English)

    Haris M Khan; Fatima Shujatullah; Mohammad Ashfaq; Adil Raza

    2011-01-01

    Objective: To determine the prevalence of malaria in Aligarh and analyze species dominance in different years over a decade. Methods: Diagnosis of malaria was done using microscopy as gold standard, rapid antigen detection assays and quantitative buffy coat (QBC) assays. Giemsa stained blood smear examination was done, thick and thin films were examined for presence of different Plasmodium spp. Rapid antigen detection assays employing detection of HRP-2 and parasite lactate dehydrogenase antigen (pLDH) by immunochromatography was done in patients whose blood smear found to be negative by conventional Giemsa slide examination. QBC was done in cases where there is strong clinical suspicion of malaria with blood smear negative, in patients with chronic malaria, splenomegaly, or in those patients who had inadequate treatment and for post-treatment follow up. Results: Plasmodium vivax and Plasmodium falciparum were only species detected in our hospital. Overall prevalence of malaria in Aligarh was found to be 8.8%. The maximum prevalence of 20.1% was observed in year 2008 and lowest 2.3% in 2002.Conclusions:High prevalence of malaria is observed in this part of country with dominance of both species particularly Plasmodium falciparum should be monitored and factors accounting for occurrence should be studied to employ effective control measures.

  1. P. berghei telomerase subunit TERT is essential for parasite survival.

    Science.gov (United States)

    Religa, Agnieszka A; Ramesar, Jai; Janse, Chris J; Scherf, Artur; Waters, Andrew P

    2014-01-01

    Telomeres define the ends of chromosomes protecting eukaryotic cells from chromosome instability and eventual cell death. The complex regulation of telomeres involves various proteins including telomerase, which is a specialized ribonucleoprotein responsible for telomere maintenance. Telomeres of chromosomes of malaria parasites are kept at a constant length during blood stage proliferation. The 7-bp telomere repeat sequence is universal across different Plasmodium species (GGGTTT/CA), though the average telomere length varies. The catalytic subunit of telomerase, telomerase reverse transcriptase (TERT), is present in all sequenced Plasmodium species and is approximately three times larger than other eukaryotic TERTs. The Plasmodium RNA component of TERT has recently been identified in silico. A strategy to delete the gene encoding TERT via double cross-over (DXO) homologous recombination was undertaken to study the telomerase function in P. berghei. Expression of both TERT and the RNA component (TR) in P. berghei blood stages was analysed by Western blotting and Northern analysis. Average telomere length was measured in several Plasmodium species using Telomere Restriction Fragment (TRF) analysis. TERT and TR were detected in blood stages and an average telomere length of ∼ 950 bp established. Deletion of the tert gene was performed using standard transfection methodologies and we show the presence of tert- mutants in the transfected parasite populations. Cloning of tert- mutants has been attempted multiple times without success. Thorough analysis of the transfected parasite populations and the parasite obtained from extensive parasite cloning from these populations provide evidence for a so called delayed death phenotype as observed in different organisms lacking TERT. The findings indicate that TERT is essential for P. berghei cell survival. The study extends our current knowledge on telomere biology in malaria parasites and validates further investigations to

  2. P. berghei telomerase subunit TERT is essential for parasite survival.

    Directory of Open Access Journals (Sweden)

    Agnieszka A Religa

    Full Text Available Telomeres define the ends of chromosomes protecting eukaryotic cells from chromosome instability and eventual cell death. The complex regulation of telomeres involves various proteins including telomerase, which is a specialized ribonucleoprotein responsible for telomere maintenance. Telomeres of chromosomes of malaria parasites are kept at a constant length during blood stage proliferation. The 7-bp telomere repeat sequence is universal across different Plasmodium species (GGGTTT/CA, though the average telomere length varies. The catalytic subunit of telomerase, telomerase reverse transcriptase (TERT, is present in all sequenced Plasmodium species and is approximately three times larger than other eukaryotic TERTs. The Plasmodium RNA component of TERT has recently been identified in silico. A strategy to delete the gene encoding TERT via double cross-over (DXO homologous recombination was undertaken to study the telomerase function in P. berghei. Expression of both TERT and the RNA component (TR in P. berghei blood stages was analysed by Western blotting and Northern analysis. Average telomere length was measured in several Plasmodium species using Telomere Restriction Fragment (TRF analysis. TERT and TR were detected in blood stages and an average telomere length of ∼ 950 bp established. Deletion of the tert gene was performed using standard transfection methodologies and we show the presence of tert- mutants in the transfected parasite populations. Cloning of tert- mutants has been attempted multiple times without success. Thorough analysis of the transfected parasite populations and the parasite obtained from extensive parasite cloning from these populations provide evidence for a so called delayed death phenotype as observed in different organisms lacking TERT. The findings indicate that TERT is essential for P. berghei cell survival. The study extends our current knowledge on telomere biology in malaria parasites and validates further

  3. Comparative genomics of the neglected human malaria parasite Plasmodium vivax

    Science.gov (United States)

    Carlton, Jane M.; Adams, John H.; Silva, Joana C.; Bidwell, Shelby L.; Lorenzi, Hernan; Caler, Elisabet; Crabtree, Jonathan; Angiuoli, Samuel V.; Merino, Emilio F.; Amedeo, Paolo; Cheng, Qin; Coulson, Richard M. R.; Crabb, Brendan S.; del Portillo, Hernando A.; Essien, Kobby; Feldblyum, Tamara V.; Fernandez-Becerra, Carmen; Gilson, Paul R.; Gueye, Amy H.; Guo, Xiang; Kang’a, Simon; Kooij, Taco W. A.; Korsinczky, Michael; Meyer, Esmeralda V.-S.; Nene, Vish; Paulsen, Ian; White, Owen; Ralph, Stuart A.; Ren, Qinghu; Sargeant, Tobias J.; Salzberg, Steven L.; Stoeckert, Christian J.; Sullivan, Steven A.; Yamamoto, Marcio Massao; Hoffman, Stephen L.; Wortman, Jennifer R.; Gardner, Malcolm J.; Galinski, Mary R.; Barnwell, John W.; Fraser-Liggett, Claire M.

    2008-01-01

    The human malaria parasite Plasmodium vivax is responsible for 25-40% of the ~515 million annual cases of malaria worldwide. Although seldom fatal, the parasite elicits severe and incapacitating clinical symptoms and often relapses months after a primary infection has cleared. Despite its importance as a major human pathogen, P. vivax is little studied because it cannot be propagated in the laboratory except in non-human primates. We determined the genome sequence of P. vivax in order to shed light on its distinctive biologic features, and as a means to drive development of new drugs and vaccines. Here we describe the synteny and isochore structure of P. vivax chromosomes, and show that the parasite resembles other malaria parasites in gene content and metabolic potential, but possesses novel gene families and potential alternate invasion pathways not recognized previously. Completion of the P. vivax genome provides the scientific community with a valuable resource that can be used to advance scientific investigation into this neglected species. PMID:18843361

  4. Plasmodium falciparum malaria in infants under 5 kg: retrospective surveillance of hospital records in five sub-saharan African countries.

    Science.gov (United States)

    Alao, Maroufou J; Gbadoé, Adama D; Meremikwu, Martin; Tshefu, Antoinette; Tiono, Alfred B; Cousin, Marc; Hamed, Kamal

    2013-04-01

    To investigate the disease burden, clinical features, treatment and outcomes of Plasmodium falciparum malaria in neonates and infants weighing Plasmodium falciparum malaria exists in this subpopulation. Further epidemiological data are needed to estimate malaria morbidity and mortality in young infants. Moreover, clinical evidence on the efficacy and safety of artemisinin-based combination therapies in this subpopulation is warranted.

  5. Cytokine balance in human malaria: does Plasmodium vivax elicit more inflammatory responses than Plasmodium falciparum?

    Directory of Open Access Journals (Sweden)

    Raquel M Gonçalves

    Full Text Available BACKGROUND: The mechanisms by which humans regulate pro- and anti-inflammatory responses on exposure to different malaria parasites remains unclear. Although Plasmodium vivax usually causes a relatively benign disease, this parasite has been suggested to elicit more host inflammation per parasitized red blood cell than P. falciparum. METHODOLOGY/PRINCIPAL FINDINGS: We measured plasma concentrations of seven cytokines and two soluble tumor necrosis factor (TNF-α receptors, and evaluated clinical and laboratory outcomes, in Brazilians with acute uncomplicated infections with P. vivax (n = 85, P. falciparum (n = 30, or both species (n = 12, and in 45 asymptomatic carriers of low-density P. vivax infection. Symptomatic vivax malaria patients, compared to those infected with P. falciparum or both species, had more intense paroxysms, but they had no clear association with a pro-inflammatory imbalance. To the contrary, these patients had higher levels of the regulatory cytokine interleukin (IL-10, which correlated positively with parasite density, and elevated IL-10/TNF-α, IL-10/interferon (IFN-γ, IL-10/IL-6 and sTNFRII/TNF-α ratios, compared to falciparum or mixed-species malaria patient groups. Vivax malaria patients had the highest levels of circulating soluble TNF-α receptor sTNFRII. Levels of regulatory cytokines returned to normal values 28 days after P. vivax clearance following chemotherapy. Finally, asymptomatic carriers of low P. vivax parasitemias had substantially lower levels of both inflammatory and regulatory cytokines than did patients with clinical malaria due to either species. CONCLUSIONS: Controlling fast-multiplying P. falciparum blood stages requires a strong inflammatory response to prevent fulminant infections, while reducing inflammation-related tissue damage with early regulatory cytokine responses may be a more cost-effective strategy in infections with the less virulent P. vivax parasite. The early induction

  6. A new world malaria map: Plasmodium falciparum endemicity in 2010

    Directory of Open Access Journals (Sweden)

    Gething Peter W

    2011-12-01

    Full Text Available Abstract Background Transmission intensity affects almost all aspects of malaria epidemiology and the impact of malaria on human populations. Maps of transmission intensity are necessary to identify populations at different levels of risk and to evaluate objectively options for disease control. To remain relevant operationally, such maps must be updated frequently. Following the first global effort to map Plasmodium falciparum malaria endemicity in 2007, this paper describes the generation of a new world map for the year 2010. This analysis is extended to provide the first global estimates of two other metrics of transmission intensity for P. falciparum that underpin contemporary questions in malaria control: the entomological inoculation rate (PfEIR and the basic reproductive number (PfR. Methods Annual parasite incidence data for 13,449 administrative units in 43 endemic countries were sourced to define the spatial limits of P. falciparum transmission in 2010 and 22,212 P. falciparum parasite rate (PfPR surveys were used in a model-based geostatistical (MBG prediction to create a continuous contemporary surface of malaria endemicity within these limits. A suite of transmission models were developed that link PfPR to PfEIR and PfR and these were fitted to field data. These models were combined with the PfPR map to create new global predictions of PfEIR and PfR. All output maps included measured uncertainty. Results An estimated 1.13 and 1.44 billion people worldwide were at risk of unstable and stable P. falciparum malaria, respectively. The majority of the endemic world was predicted with a median PfEIR of less than one and a median PfRc of less than two. Values of either metric exceeding 10 were almost exclusive to Africa. The uncertainty described in both PfEIR and PfR was substantial in regions of intense transmission. Conclusions The year 2010 has a particular significance as an evaluation milestone for malaria global health policy. The

  7. Malaria-like symptoms associated with a natural Plasmodium reichenowi infection in a chimpanzee.

    Science.gov (United States)

    Herbert, Anaïs; Boundenga, Larson; Meyer, Anne; Moukodoum, Diamella Nancy; Okouga, Alain Prince; Arnathau, Céline; Durand, Patrick; Magnus, Julie; Ngoubangoye, Barthélémy; Willaume, Eric; Ba, Cheikh Tidiane; Rougeron, Virginie; Renaud, François; Ollomo, Benjamin; Prugnolle, Franck

    2015-05-28

    Although Plasmodium infections have never been clearly associated with symptoms in non-human primates, the question of the pathogenicity of Plasmodium parasites in non-human primates still remains unanswered. A young chimpanzee, followed before and after release to a sanctuary, in a semi-free ranging enclosure located in an equatorial forest, showed fever and strong anaemia associated with a high Plasmodium reichenowi infection, shortly after release. The animal recovered from anaemia after several months despite recurrent infection with other Plasmodium species. This may be the first description of malaria-like symptoms in a chimpanzee infected with Plasmodium.

  8. Longevity and composition of cellular immune responses following experimental Plasmodium falciparum malaria infection in humans.

    NARCIS (Netherlands)

    Teirlinck, A.C.; McCall, M.B.B.; Roestenberg, M.; Scholzen, A.; Woestenenk, R.M.; Mast, Q. de; Ven, A.J.A.M. van der; Hermsen, C.C.; Luty, A.J.F.; Sauerwein, R.W.

    2011-01-01

    Cellular responses to Plasmodium falciparum parasites, in particular interferon-gamma (IFNgamma) production, play an important role in anti-malarial immunity. However, clinical immunity to malaria develops slowly amongst naturally exposed populations, the dynamics of cellular responses in relation

  9. Drug resistance to sulphadoxine-pyrimethamine in Plasmodium falciparum malaria in Mlimba, Tanzania

    NARCIS (Netherlands)

    Mbugi, E.V.; Mutayoba, B.M.; Malisa, A.L.; Balthazary, S.T.; Nyambo, T.B.; Mshinda, H.

    2006-01-01

    Background - Sulphadoxine-pyrimethamine (SP) has been and is currently used for treatment of uncomplicated Plasmodium falciparum malaria in many African countries. Nevertheless, the response of parasites to SP treatment has shown significant variation between individuals. Methods - The genes for

  10. Molecular epidemiology of Plasmodium vivax and Plasmodium falciparum malaria among Duffy-positive and Duffy-negative populations in Ethiopia.

    Science.gov (United States)

    Lo, Eugenia; Yewhalaw, Delenasaw; Zhong, Daibin; Zemene, Endalew; Degefa, Teshome; Tushune, Kora; Ha, Margaret; Lee, Ming-Chieh; James, Anthony A; Yan, Guiyun

    2015-02-19

    Malaria is the most prevalent communicable disease in Ethiopia, with 75% of the country's landmass classified as endemic for malaria. Accurate information on the distribution and clinical prevalence of Plasmodium vivax and Plasmodium falciparum malaria in endemic areas, as well as in Duffy-negative populations, is essential to develop integrated control strategies. A total of 390 and 416 community and clinical samples, respectively, representing different localities and age groups across Ethiopia were examined. Malaria prevalence was estimated using nested PCR of the 18S rRNA region. Parasite gene copy number was measured by quantitative real-time PCR and compared between symptomatic and asymptomatic samples, as well as between children/adolescents and adults from the local community. An approximately 500-bp segment of the human DARC gene was amplified and sequenced to identify Duffy genotype at the -33rd nucleotide position for all the clinical and community samples. Plasmodium vivax prevalence was higher in the south while P. falciparum was higher in the north. The prevalence of P. vivax and P. falciparum malaria is the highest in children compared to adolescents and adults. Four P. vivax infections were detected among the Duffy-negative samples. Samples from asymptomatic individuals show a significantly lower parasite gene copy number than those from symptomatic infections for P. vivax and P. falciparum. Geographical and age differences influence the distribution of P. vivax and P. falciparum malaria in Ethiopia. These findings offer evidence-based guidelines in targeting malaria control efforts in the country.

  11. Avian malaria on Madagascar: bird hosts and putative vector mosquitoes of different Plasmodium lineages.

    Science.gov (United States)

    Schmid, Sandrine; Dinkel, Anke; Mackenstedt, Ute; Tantely, Michaël Luciano; Randrianambinintsoa, Fano José; Boyer, Sébastien; Woog, Friederike

    2017-01-05

    Avian malaria occurs almost worldwide and is caused by Haemosporida parasites (Plasmodium, Haemoproteus and Leucocytozoon). Vectors such as mosquitoes, hippoboscid flies or biting midges are required for the transmission of these parasites. There are few studies about avian malaria parasites on Madagascar but none about suitable vectors. To identify vectors of avian Plasmodium parasites on Madagascar, we examined head, thorax and abdomen of 418 mosquitoes from at least 18 species using a nested PCR method to amplify a 524 bp fragment of the haemosporidian mitochondrial cytochrome b gene. Sequences obtained were then compared with a large dataset of haemosporidian sequences detected in 45 different bird species (n = 686) from the same area in the Maromizaha rainforest. Twenty-one mosquitoes tested positive for avian malaria parasites. Haemoproteus DNA was found in nine mosquitoes (2.15%) while Plasmodium DNA was found in 12 mosquitoes (2.87%). Seven distinct lineages were identified among the Plasmodium DNA samples. Some lineages were also found in the examined bird samples: Plasmodium sp. WA46 (EU810628.1) in the Madagascar bulbul, Plasmodium sp. mosquito 132 (AB308050.1) in 15 bird species belonging to eight families, Plasmodium sp. PV12 (GQ150194.1) in eleven bird species belonging to eight families and Plasmodium sp. P31 (DQ839060.1) was found in three weaver bird species. This study provides the first insight into avian malaria transmission in the Maromizaha rainforest in eastern Madagascar. Five Haemoproteus lineages and seven Plasmodium lineages were detected in the examined mosquitoes. Complete life-cycles for the specialist lineages WA46 and P31 and for the generalist lineages mosquito132 and PV12 of Plasmodium are proposed. In addition, we have identified for the first time Anopheles mascarensis and Uranotaenia spp. as vectors for avian malaria and offer the first description of vector mosquitoes for avian malaria in Madagascar.

  12. A World Malaria Map: Plasmodium falciparum Endemicity in 2007

    Science.gov (United States)

    Hay, Simon I; Guerra, Carlos A; Gething, Peter W; Patil, Anand P; Tatem, Andrew J; Noor, Abdisalan M; Kabaria, Caroline W; Manh, Bui H; Elyazar, Iqbal R. F; Brooker, Simon; Smith, David L; Moyeed, Rana A; Snow, Robert W

    2009-01-01

    Background Efficient allocation of resources to intervene against malaria requires a detailed understanding of the contemporary spatial distribution of malaria risk. It is exactly 40 y since the last global map of malaria endemicity was published. This paper describes the generation of a new world map of Plasmodium falciparum malaria endemicity for the year 2007. Methods and Findings A total of 8,938 P. falciparum parasite rate (PfPR) surveys were identified using a variety of exhaustive search strategies. Of these, 7,953 passed strict data fidelity tests for inclusion into a global database of PfPR data, age-standardized to 2–10 y for endemicity mapping. A model-based geostatistical procedure was used to create a continuous surface of malaria endemicity within previously defined stable spatial limits of P. falciparum transmission. These procedures were implemented within a Bayesian statistical framework so that the uncertainty of these predictions could be evaluated robustly. The uncertainty was expressed as the probability of predicting correctly one of three endemicity classes; previously stratified to be an informative guide for malaria control. Population at risk estimates, adjusted for the transmission modifying effects of urbanization in Africa, were then derived with reference to human population surfaces in 2007. Of the 1.38 billion people at risk of stable P. falciparum malaria, 0.69 billion were found in Central and South East Asia (CSE Asia), 0.66 billion in Africa, Yemen, and Saudi Arabia (Africa+), and 0.04 billion in the Americas. All those exposed to stable risk in the Americas were in the lowest endemicity class (PfPR2−10 ≤ 5%). The vast majority (88%) of those living under stable risk in CSE Asia were also in this low endemicity class; a small remainder (11%) were in the intermediate endemicity class (PfPR2−10 > 5 to < 40%); and the remaining fraction (1%) in high endemicity (PfPR2−10 ≥ 40%) areas. High endemicity was widespread in the

  13. Hemoglobinopathies: slicing the Gordian knot of Plasmodium falciparum malaria pathogenesis.

    Science.gov (United States)

    Taylor, Steve M; Cerami, Carla; Fairhurst, Rick M

    2013-01-01

    Plasmodium falciparum malaria kills over 500,000 children every year and has been a scourge of humans for millennia. Owing to the co-evolution of humans and P. falciparum parasites, the human genome is imprinted with polymorphisms that not only confer innate resistance to falciparum malaria, but also cause hemoglobinopathies. These genetic traits--including hemoglobin S (HbS), hemoglobin C (HbC), and α-thalassemia--are the most common monogenic human disorders and can confer remarkable degrees of protection from severe, life-threatening falciparum malaria in African children: the risk is reduced 70% by homozygous HbC and 90% by heterozygous HbS (sickle-cell trait). Importantly, this protection is principally present for severe disease and largely absent for P. falciparum infection, suggesting that these hemoglobinopathies specifically neutralize the parasite's in vivo mechanisms of pathogenesis. These hemoglobin variants thus represent a "natural experiment" to identify the cellular and molecular mechanisms by which P. falciparum produces clinical morbidity, which remain partially obscured due to the complexity of interactions between this parasite and its human host. Multiple lines of evidence support a restriction of parasite growth by various hemoglobinopathies, and recent data suggest this phenomenon may result from host microRNA interference with parasite metabolism. Multiple hemoglobinopathies mitigate the pathogenic potential of parasites by interfering with the export of P. falciparum erythrocyte membrane protein 1 (PfEMP1) to the surface of the host red blood cell. Few studies have investigated their effects upon the activation of the innate and adaptive immune systems, although recent murine studies suggest a role for heme oxygenase-1 in protection. Ultimately, the identification of mechanisms of protection and pathogenesis can inform future therapeutics and preventive measures. Hemoglobinopathies slice the "Gordian knot" of host and parasite

  14. Hemoglobinopathies: Slicing the Gordian Knot of Plasmodium falciparum Malaria Pathogenesis

    Science.gov (United States)

    Taylor, Steve M.; Cerami, Carla; Fairhurst, Rick M.

    2013-01-01

    Plasmodium falciparum malaria kills over 500,000 children every year and has been a scourge of humans for millennia. Owing to the co-evolution of humans and P. falciparum parasites, the human genome is imprinted with polymorphisms that not only confer innate resistance to falciparum malaria, but also cause hemoglobinopathies. These genetic traits—including hemoglobin S (HbS), hemoglobin C (HbC), and α-thalassemia—are the most common monogenic human disorders and can confer remarkable degrees of protection from severe, life-threatening falciparum malaria in African children: the risk is reduced 70% by homozygous HbC and 90% by heterozygous HbS (sickle-cell trait). Importantly, this protection is principally present for severe disease and largely absent for P. falciparum infection, suggesting that these hemoglobinopathies specifically neutralize the parasite's in vivo mechanisms of pathogenesis. These hemoglobin variants thus represent a “natural experiment” to identify the cellular and molecular mechanisms by which P. falciparum produces clinical morbidity, which remain partially obscured due to the complexity of interactions between this parasite and its human host. Multiple lines of evidence support a restriction of parasite growth by various hemoglobinopathies, and recent data suggest this phenomenon may result from host microRNA interference with parasite metabolism. Multiple hemoglobinopathies mitigate the pathogenic potential of parasites by interfering with the export of P. falciparum erythrocyte membrane protein 1 (PfEMP1) to the surface of the host red blood cell. Few studies have investigated their effects upon the activation of the innate and adaptive immune systems, although recent murine studies suggest a role for heme oxygenase-1 in protection. Ultimately, the identification of mechanisms of protection and pathogenesis can inform future therapeutics and preventive measures. Hemoglobinopathies slice the “Gordian knot” of host and parasite

  15. Hemoglobinopathies: slicing the Gordian knot of Plasmodium falciparum malaria pathogenesis.

    Directory of Open Access Journals (Sweden)

    Steve M Taylor

    Full Text Available Plasmodium falciparum malaria kills over 500,000 children every year and has been a scourge of humans for millennia. Owing to the co-evolution of humans and P. falciparum parasites, the human genome is imprinted with polymorphisms that not only confer innate resistance to falciparum malaria, but also cause hemoglobinopathies. These genetic traits--including hemoglobin S (HbS, hemoglobin C (HbC, and α-thalassemia--are the most common monogenic human disorders and can confer remarkable degrees of protection from severe, life-threatening falciparum malaria in African children: the risk is reduced 70% by homozygous HbC and 90% by heterozygous HbS (sickle-cell trait. Importantly, this protection is principally present for severe disease and largely absent for P. falciparum infection, suggesting that these hemoglobinopathies specifically neutralize the parasite's in vivo mechanisms of pathogenesis. These hemoglobin variants thus represent a "natural experiment" to identify the cellular and molecular mechanisms by which P. falciparum produces clinical morbidity, which remain partially obscured due to the complexity of interactions between this parasite and its human host. Multiple lines of evidence support a restriction of parasite growth by various hemoglobinopathies, and recent data suggest this phenomenon may result from host microRNA interference with parasite metabolism. Multiple hemoglobinopathies mitigate the pathogenic potential of parasites by interfering with the export of P. falciparum erythrocyte membrane protein 1 (PfEMP1 to the surface of the host red blood cell. Few studies have investigated their effects upon the activation of the innate and adaptive immune systems, although recent murine studies suggest a role for heme oxygenase-1 in protection. Ultimately, the identification of mechanisms of protection and pathogenesis can inform future therapeutics and preventive measures. Hemoglobinopathies slice the "Gordian knot" of host and

  16. RELATIONSHIP OF HEPATIC AND RENAL DYSFUNCTION WITH HAEMORRHEOLOGICAL PARAMETERS IN PLASMODIUM FALCIPARUM MALARIA

    Directory of Open Access Journals (Sweden)

    Valluri Satya

    2015-04-01

    Full Text Available The clinical pattern of malaria has changed worldwide including India in last decade. Earlier cerebral malaria was the predominant manifestation of severe malaria, whereas now the combination of jaundice and renal failure are more common. Severe haemorrhage is seen in upto 5% of patients with severe malaria. Studies on renal and hepatic dys function in Plasmodium falciparum malaria are a plenty, but there is a paucity of studies correlating haemorrheological abnormalities with hepatic and renal dysfunction in Plasmodium falciparum malaria. METHODS : 100 patients of malaria with positive periph eral blood smear for plasmodium falciparum , out of which 50 cases with AKI and Hepatic failure during the period January 2012 - June 2013. I n department of general medicine, Government General Hospital, Kakinada. GROUP A : Comprising 50 consecutive adult pat ients of all age groups and both genders who had jaundice or renal failure or both at the time of admission. GROUP B: comprising 50 consecutive cases of plasmodium falciparum malaria and had no complications. RESULTS: In group A patients all parameters are significantly raised as compared to group B patients. CONCLUSION: 10% of patients had clinically overt bleeding manifestations, this indicates subclinical haemorrheological dysfunction in patients suffering from falciparum malaria with hepatic and renal d ysfunction, high incidence of subclinical DIC, evidenced by prolonged aPTT (56%, low total platelet count (58%, and PT (20%. An observational, screening, analytical prospective study. 100 cases of PF positive complicated and uncomplicated cases during t he period - January 2012 - June 2013

  17. A 20-year longitudinal study of Plasmodium ovale and Plasmodium malariae prevalence and morbidity in a West African population.

    Directory of Open Access Journals (Sweden)

    Clémentine Roucher

    Full Text Available BACKGROUND: Plasmodium ovale and Plasmodium malariae have long been reported to be widely distributed in tropical Africa and in other major malaria-endemic areas of the world. However, little is known about the burden caused by these two malaria species. METHODS AND FINDINGS: We did a longitudinal study of the inhabitants of Dielmo village, Senegal, between June, 1990, and December, 2010. We monitored the inhabitants for fever during this period and performed quarterly measurements of parasitemia. We analyzed parasitological and clinical data in a random-effect logistic regression model to investigate the relationship between the level of parasitemia and the risk of fever and to establish diagnostic criteria for P. ovale and P. malariae clinical attacks. The prevalence of P. ovale and P. malariae infections in asymptomatic individuals were high during the first years of the project but decreased after 2004 and almost disappeared in 2010 in relation to changes in malaria control policies. The average incidence densities of P. ovale and P. malariae clinical attacks were 0.053 and 0.093 attacks per person per year in children <15 years and 0.024 and 0.009 attacks per person per year in adults ≥ 15 years, respectively. These two malaria species represented together 5.9% of the malaria burden. CONCLUSIONS: P. ovale and P. malariae were a common cause of morbidity in Dielmo villagers until the recent dramatic decrease of malaria that followed the introduction of new malaria control policies. P. ovale and P. malariae may constitute an important cause of morbidity in many areas of tropical Africa.

  18. Plasmodium falciparum Malaria Endemicity in Indonesia in 2010

    Science.gov (United States)

    Elyazar, Iqbal R. F.; Gething, Peter W.; Patil, Anand P.; Rogayah, Hanifah; Kusriastuti, Rita; Wismarini, Desak M.; Tarmizi, Siti N.; Baird, J. Kevin; Hay, Simon I.

    2011-01-01

    Background Malaria control programs require a detailed understanding of the contemporary spatial distribution of infection risk to efficiently allocate resources. We used model based geostatistics (MBG) techniques to generate a contemporary map of Plasmodium falciparum malaria risk in Indonesia in 2010. Methods Plasmodium falciparum Annual Parasite Incidence (PfAPI) data (2006–2008) were used to map limits of P. falciparum transmission. A total of 2,581 community blood surveys of P. falciparum parasite rate (PfPR) were identified (1985–2009). After quality control, 2,516 were included into a national database of age-standardized 2–10 year old PfPR data (PfPR2–10) for endemicity mapping. A Bayesian MBG procedure was used to create a predicted surface of PfPR2–10 endemicity with uncertainty estimates. Population at risk estimates were derived with reference to a 2010 human population count surface. Results We estimate 132.8 million people in Indonesia, lived at risk of P. falciparum transmission in 2010. Of these, 70.3% inhabited areas of unstable transmission and 29.7% in stable transmission. Among those exposed to stable risk, the vast majority were at low risk (93.39%) with the reminder at intermediate (6.6%) and high risk (0.01%). More people in western Indonesia lived in unstable rather than stable transmission zones. In contrast, fewer people in eastern Indonesia lived in unstable versus stable transmission areas. Conclusion While further feasibility assessments will be required, the immediate prospects for sustained control are good across much of the archipelago and medium term plans to transition to the pre-elimination phase are not unrealistic for P. falciparum. Endemicity in areas of Papua will clearly present the greatest challenge. This P. falciparum endemicity map allows malaria control agencies and their partners to comprehensively assess the region-specific prospects for reaching pre-elimination, monitor and evaluate the effectiveness of

  19. Effect of meteorological variables on Plasmodium vivax and Plasmodium falciparum malaria in outbreak prone districts of Rajasthan, India.

    Science.gov (United States)

    Lingala, Mercy A L

    2017-03-09

    Malaria is a public health problem caused by Plasmodium parasite and transmitted by anopheline mosquitoes. Arid and semi-arid regions of western India are prone to malaria outbreaks. Malaria outbreak prone districts viz. Bikaner, Barmer and Jodhpur were selected to study the effect of meteorological variables on Plasmodium vivax and Plasmodium falciparum malaria outbreaks for the period of 2009-2012. The data of monthly malaria cases and meteorological variables was analysed using SPSS 20v. Spearman correlation analysis was conducted to examine the strength of the relationship between meteorological variables, P. vivax and P. falciparum malaria cases. Pearson's correlation analysis was carried out among the meteorological variables to observe the independent effect of each independent variable on the outcome. Results indicate that malaria outbreaks have occurred in Bikaner and Barmer due to continuous rains for more than two months. Rainfall has shown to be an important predictor of malaria outbreaks in Rajasthan. P. vivax is more significantly correlated with rainfall, minimum temperature (P<0.01) and less significantly with relative humidity (P<0.05); whereas P. falciparum is significantly correlated with rainfall, relative humidity (P<0.01) and less significantly with temperature (P<0.05). The determination of the lag period for P. vivax is relative humidity and for P. falciparum is temperature. The lag period between malaria cases and rainfall is shorter for P. vivax than P. falciparum. In conclusion, the knowledge generated is not only useful to take prompt malaria control interventions but also helpful to develop better forecasting model in outbreak prone regions. Copyright © 2017 The Author. Published by Elsevier Ltd.. All rights reserved.

  20. Plasmodium cynomolgi genome sequences provide insight into Plasmodium vivax and the monkey malaria clade.

    Science.gov (United States)

    Tachibana, Shin-Ichiro; Sullivan, Steven A; Kawai, Satoru; Nakamura, Shota; Kim, Hyunjae R; Goto, Naohisa; Arisue, Nobuko; Palacpac, Nirianne M Q; Honma, Hajime; Yagi, Masanori; Tougan, Takahiro; Katakai, Yuko; Kaneko, Osamu; Mita, Toshihiro; Kita, Kiyoshi; Yasutomi, Yasuhiro; Sutton, Patrick L; Shakhbatyan, Rimma; Horii, Toshihiro; Yasunaga, Teruo; Barnwell, John W; Escalante, Ananias A; Carlton, Jane M; Tanabe, Kazuyuki

    2012-09-01

    P. cynomolgi, a malaria-causing parasite of Asian Old World monkeys, is the sister taxon of P. vivax, the most prevalent malaria-causing species in humans outside of Africa. Because P. cynomolgi shares many phenotypic, biological and genetic characteristics with P. vivax, we generated draft genome sequences for three P. cynomolgi strains and performed genomic analysis comparing them with the P. vivax genome, as well as with the genome of a third previously sequenced simian parasite, Plasmodium knowlesi. Here, we show that genomes of the monkey malaria clade can be characterized by copy-number variants (CNVs) in multigene families involved in evasion of the human immune system and invasion of host erythrocytes. We identify genome-wide SNPs, microsatellites and CNVs in the P. cynomolgi genome, providing a map of genetic variation that can be used to map parasite traits and study parasite populations. The sequencing of the P. cynomolgi genome is a critical step in developing a model system for P. vivax research and in counteracting the neglect of P. vivax.

  1. Molecular Detection of Plasmodium malariae/Plasmodium brasilianum in Non-Human Primates in Captivity in Costa Rica.

    Science.gov (United States)

    Fuentes-Ramírez, Alicia; Jiménez-Soto, Mauricio; Castro, Ruth; Romero-Zuñiga, Juan José; Dolz, Gaby

    2017-01-01

    One hundred and fifty-two blood samples of non-human primates of thirteen rescue centers in Costa Rica were analyzed to determine the presence of species of Plasmodium using thick blood smears, semi-nested multiplex polymerase chain reaction (SnM-PCR) for species differentiation, cloning and sequencing for confirmation. Using thick blood smears, two samples were determined to contain the Plasmodium malariae parasite, with SnM-PCR, a total of five (3.3%) samples were positive to P. malariae, cloning and sequencing confirmed both smear samples as P. malariae. One sample amplified a larger and conserved region of 18S rDNA for the genus Plasmodium and sequencing confirmed the results obtained microscopically and through SnM-PCR tests. Sequencing and construction of a phylogenetic tree of this sample revealed that the P. malariae/P. brasilianum parasite (GenBank KU999995) found in a howler monkey (Alouatta palliata) is identical to that recently reported in humans in Costa Rica. The SnM-PCR detected P. malariae/P. brasilianum parasite in different non-human primate species in captivity and in various regions of the southern Atlantic and Pacific coast of Costa Rica. The similarity of the sequences of parasites found in humans and a monkey suggests that monkeys may be acting as reservoirs of P.malariae/P. brasilianum, for which reason it is important, to include them in control and eradication programs.

  2. Molecular Detection of Plasmodium malariae/Plasmodium brasilianum in Non-Human Primates in Captivity in Costa Rica

    Science.gov (United States)

    Fuentes-Ramírez, Alicia; Jiménez-Soto, Mauricio; Castro, Ruth; Romero-Zuñiga, Juan José

    2017-01-01

    One hundred and fifty-two blood samples of non-human primates of thirteen rescue centers in Costa Rica were analyzed to determine the presence of species of Plasmodium using thick blood smears, semi-nested multiplex polymerase chain reaction (SnM-PCR) for species differentiation, cloning and sequencing for confirmation. Using thick blood smears, two samples were determined to contain the Plasmodium malariae parasite, with SnM-PCR, a total of five (3.3%) samples were positive to P. malariae, cloning and sequencing confirmed both smear samples as P. malariae. One sample amplified a larger and conserved region of 18S rDNA for the genus Plasmodium and sequencing confirmed the results obtained microscopically and through SnM-PCR tests. Sequencing and construction of a phylogenetic tree of this sample revealed that the P. malariae/P. brasilianum parasite (GenBank KU999995) found in a howler monkey (Alouatta palliata) is identical to that recently reported in humans in Costa Rica. The SnM-PCR detected P. malariae/P. brasilianum parasite in different non-human primate species in captivity and in various regions of the southern Atlantic and Pacific coast of Costa Rica. The similarity of the sequences of parasites found in humans and a monkey suggests that monkeys may be acting as reservoirs of P.malariae/P. brasilianum, for which reason it is important, to include them in control and eradication programs. PMID:28125696

  3. Modulatory effect of crude aqueous extract of Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Higher Basidiomycetes), on hematological and antioxidant indices in Plasmodium berghei-infected mice.

    Science.gov (United States)

    Oluba, Olarewaju M; Adebisi, Kayode E; Eidangbe, George O; Odutuga, Adewale A; Onyeneke, E Chukwu

    2014-01-01

    Hematological and antioxidant effects of the aqueous extract of fruiting bodies of Ganoderma lucidum were evaluated in Plasmodium berghei-infected mice. Extract was administered at doses of 100, 250, and 500 mg/kg body weight by an intragastric tube once daily for 14 d starting from the fourth day after parasite inoculation. At the end of treatment period, mice in each group were sacrificed and blood was collected for hematological and biochemical analyses. A significant (P<0.05) decrease was observed in serum malondialdehyde content with a corresponding significant (P<0.05) increase in superoxide dismutase, glutathione peroxidase, glutathione S-transferase, and glucose 6-phosphate dehydrogenase activities in the extract-treated groups compared to the infected but untreated group. The results obtained suggest that crude aqueous extract of G. lucidum fruiting bodies possesses potent antioxidant activity that protects hemoglobin against Plasmodium-induced oxidative damage. These findings seem to justify the use of the plant in traditional African and Chinese medicine as an anti-inflammatory and antimicrobial agent.

  4. The ¿/d T-cell response to Plasmodium falciparum malaria in a population in which malaria is endemic

    DEFF Research Database (Denmark)

    Hviid, L; Kurtzhals, J A; Dodoo, D

    1996-01-01

    Frequencies and absolute numbers of peripheral gamma/delta T cells have been reported to increase after episodes of Plasmodium falciparum malaria in adults with limited or no previous malaria exposure. In contrast, little is known about the gamma/delta T-cell response to malaria in children from......, Denmark, all with uncomplicated, primary P. falciparum malaria, showed increased gamma/delta T-cell frequencies similar to those previously reported. All patients had lowered absolute numbers of peripheral gamma/delta T cells at admission, changing to increased numbers by days 7 to 14 and then returning...

  5. Lack of Evidence for Chloroquine-Resistant Plasmodium falciparum Malaria, Leogane, Haiti

    Science.gov (United States)

    Neuberger, Ami; Zhong, Kathleen; Kain, Kevin C

    2012-01-01

    Plasmodium falciparum malaria in Haiti is considered chloroquine susceptible, although resistance transporter alleles associated with chloroquine resistance were recently detected. Among 49 patients with falciparum malaria, we found neither parasites carrying haplotypes associated with chloroquine resistance nor instances of chloroquine treatment failure. Continued vigilance to detect emergence of chloroquine resistance is needed. PMID:22932030

  6. 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...

  7. Lack of evidence for chloroquine-resistant Plasmodium falciparum malaria, Leogane, Haiti.

    Science.gov (United States)

    Neuberger, Ami; Zhong, Kathleen; Kain, Kevin C; Schwartz, Eli

    2012-09-01

    Plasmodium falciparum malaria in Haiti is considered chloroquine susceptible, although resistance transporter alleles associated with chloroquine resistance were recently detected. Among 49 patients with falciparum malaria, we found neither parasites carrying haplotypes associated with chloroquine resistance nor instances of chloroquine treatment failure. Continued vigilance to detect emergence of chloroquine resistance is needed.

  8. 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.

  9. Imported Plasmodium knowlesi malaria in a French tourist returning from Thailand.

    Science.gov (United States)

    Berry, Antoine; Iriart, Xavier; Wilhelm, Nathalie; Valentin, Alexis; Cassaing, Sophie; Witkowski, Benoit; Benoit-Vical, Françoise; Menard, Sandie; Olagnier, David; Fillaux, Judith; Sire, Stephane; Le Coustumier, Alain; Magnaval, Jean-François

    2011-04-01

    We report a case of imported Plasmodium knowlesi malaria in a French tourist following a vacation in Thailand. This case shows, first, tourists may contract knowlesi malaria even only staying on the beach and second, the diagnosis remains difficult, even with polymerase chain reaction methods.

  10. Recrudescence of Plasmodium falciparum malaria contracted in Lombok, Indonesia after quinine/doxycycline and mefloquine: case report.

    Science.gov (United States)

    Tish, K N; Pillans, P I

    1997-07-11

    A patient is reported who contracted Plasmodium falciparum malaria in Lombok, Indonesia. The infection recrudesced after quinine/doxycycline and mefloquine. Treatment with halofantrine was successful after he developed cerebral malaria with recovery.

  11. 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.

  12. Caspar controls resistance to Plasmodium falciparum in diverse anopheline species.

    OpenAIRE

    Garver, Lindsey S.; Yuemei Dong; George Dimopoulos

    2009-01-01

    Immune responses mounted by the malaria vector Anopheles gambiae are largely regulated by the Toll and Imd (immune deficiency) pathways via the NF-kappaB transcription factors Rel1 and Rel2, which are controlled by the negative regulators Cactus and Caspar, respectively. Rel1- and Rel2-dependent transcription in A. gambiae has been shown to be particularly critical to the mosquito's ability to manage infection with the rodent malaria parasite Plasmodium berghei. Using RNA interference to depl...

  13. The effects of urbanization on global Plasmodium vivax malaria transmission

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    Qi Qiuyin

    2012-12-01

    Full Text Available Abstract Background Many recent studies have examined the impact of urbanization on Plasmodium falciparum malaria endemicity and found a general trend of reduced transmission in urban areas. However, none has examined the effect of urbanization on Plasmodium vivax malaria, which is the most widely distributed malaria species and can also cause severe clinical syndromes in humans. In this study, a set of 10,003 community-based P. vivax parasite rate (PvPR surveys are used to explore the relationships between PvPR in urban and rural settings. Methods The PvPR surveys were overlaid onto a map of global urban extents to derive an urban/rural assignment. The differences in PvPR values between urban and rural areas were then examined. Groups of PvPR surveys inside individual city extents (urban and surrounding areas (rural were identified to examine the local variations in PvPR values. Finally, the relationships of PvPR between urban and rural areas within the ranges of 41 dominant Anopheles vectors were examined. Results Significantly higher PvPR values in rural areas were found globally. The relationship was consistent at continental scales when focusing on Africa and Asia only, but in the Americas, significantly lower values of PvPR in rural areas were found, though the numbers of surveys were small. Moreover, except for the countries in the Americas, the same trends were found at national scales in African and Asian countries, with significantly lower values of PvPR in urban areas. However, the patterns at city scales among 20 specific cities where sufficient data were available were less clear, with seven cities having significantly lower PvPR values in urban areas and two cities showing significantly lower PvPR in rural areas. The urban–rural PvPR differences within the ranges of the dominant Anopheles vectors were generally, in agreement with the regional patterns found. Conclusions Except for the Americas, the patterns of significantly lower

  14. 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.

  15. Chloroquine-resistant Plasmodium vivax malaria in Debre Zeit, Ethiopia

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    Muchohi Simon

    2008-10-01

    Full Text Available Abstract Background Plasmodium vivax accounts for about 40% of all malaria infection in Ethiopia. Chloroquine (CQ is the first line treatment for confirmed P. vivax malaria in the country. The first report of CQ treatment failure in P. vivax was from Debre Zeit, which suggested the presence of chloroquine resistance. Methods An in vivo drug efficacy study was conducted in Debre Zeit from June to August 2006. Eighty-seven patients with microscopically confirmed P. vivax malaria, aged between 8 months and 52 years, were recruited and treated under supervision with CQ (25 mg/kg over three days. Clinical and parasitological parameters were assessed during the 28 day follow-up period. CQ and desethylchloroquine (DCQ blood and serum concentrations were determined with high performance liquid chromatography (HPLC in patients who showed recurrent parasitaemia. Results Of the 87 patients recruited in the study, one was lost to follow-up and three were excluded due to P. falciparum infection during follow-up. A total of 83 (95% of the study participants completed the follow-up. On enrolment, 39.8% had documented fever and 60.2% had a history of fever. The geometric mean parasite density of the patients was 7045 parasites/μl. Among these, four patients had recurrent parasitaemia on Day 28. The blood CQ plus DCQ concentrations of these four patients were all above the minimal effective concentration (> 100 ng/ml. Conclusion Chloroquine-resistant P. vivax parasites are emerging in Debre Zeit, Ethiopia. A multi-centre national survey is needed to better understand the extent of P. vivax resistance to CQ in Ethiopia.

  16. A molecular mechanism of artemisinin resistance in Plasmodium falciparum malaria.

    Science.gov (United States)

    Mbengue, Alassane; Bhattacharjee, Souvik; Pandharkar, Trupti; Liu, Haining; Estiu, Guillermina; Stahelin, Robert V; Rizk, Shahir S; Njimoh, Dieudonne L; Ryan, Yana; Chotivanich, Kesinee; Nguon, Chea; Ghorbal, Mehdi; Lopez-Rubio, Jose-Juan; Pfrender, Michael; Emrich, Scott; Mohandas, Narla; Dondorp, Arjen M; Wiest, Olaf; Haldar, Kasturi

    2015-04-30

    Artemisinins are the cornerstone of anti-malarial drugs. Emergence and spread of resistance to them raises risk of wiping out recent gains achieved in reducing worldwide malaria burden and threatens future malaria control and elimination on a global level. Genome-wide association studies (GWAS) have revealed parasite genetic loci associated with artemisinin resistance. However, there is no consensus on biochemical targets of artemisinin. Whether and how these targets interact with genes identified by GWAS, remains unknown. Here we provide biochemical and cellular evidence that artemisinins are potent inhibitors of Plasmodium falciparum phosphatidylinositol-3-kinase (PfPI3K), revealing an unexpected mechanism of action. In resistant clinical strains, increased PfPI3K was associated with the C580Y mutation in P. falciparum Kelch13 (PfKelch13), a primary marker of artemisinin resistance. Polyubiquitination of PfPI3K and its binding to PfKelch13 were reduced by the PfKelch13 mutation, which limited proteolysis of PfPI3K and thus increased levels of the kinase, as well as its lipid product phosphatidylinositol-3-phosphate (PI3P). We find PI3P levels to be predictive of artemisinin resistance in both clinical and engineered laboratory parasites as well as across non-isogenic strains. Elevated PI3P induced artemisinin resistance in absence of PfKelch13 mutations, but remained responsive to regulation by PfKelch13. Evidence is presented for PI3P-dependent signalling in which transgenic expression of an additional kinase confers resistance. Together these data present PI3P as the key mediator of artemisinin resistance and the sole PfPI3K as an important target for malaria elimination.

  17. Chronic Plasmodium falciparum infections in an area of low intensity malaria transmission in the Sudan

    DEFF Research Database (Denmark)

    Hamad, A A; El Hassan, I M; El Khalifa, A A

    2000-01-01

    Chronic Plasmodium falciparum malaria infections in a Sudanese village, in an area of seasonal and unstable malaria transmission, were monitored and genetically characterized to study the influence of persistent infection on the immunology and epidemiology of low endemicity malaria. During...... the October-December malaria season of 1996, 51 individuals out of a population of 420 had confirmed and treated P. falciparum malaria in the village of Daraweesh in eastern Sudan. In a cross-sectional survey carried out in December 1996, an additional 6 individuals were found to harbour a microscopically...

  18. A case of Plasmodium vivax malaria associated with severe autoimmune hemolytic anaemia

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    Dinesh Singh

    2012-01-01

    Full Text Available Anemia in malaria is multifactorial. Autoimmune hemolysis is an extremely rare cause of anemia in malaria and more so in vivax malaria. A 35-year-old female presented to us with fever and anemia. She was diagnosed as vivax malaria with autoimmune hemolytc anemia by a positive Direct Coomb′s test. We treated her with antimalarial durgs, corticosteroids, and transfused her with the least incompatible blood. The patient recovered and was discharged. Hence, we suggest that autoimmune hemolysis be considered an important cause of anemia in Plasmodium vivax (P. vivax malaria.

  19. Spatial and space-time distribution of Plasmodium vivax and Plasmodium falciparum malaria in China, 2005-2014.

    Science.gov (United States)

    Hundessa, Samuel H; Williams, Gail; Li, Shanshan; Guo, Jinpeng; Chen, Linping; Zhang, Wenyi; Guo, Yuming

    2016-12-19

    Despite the declining burden of malaria in China, the disease remains a significant public health problem with periodic outbreaks and spatial variation across the country. A better understanding of the spatial and temporal characteristics of malaria is essential for consolidating the disease control and elimination programme. This study aims to understand the spatial and spatiotemporal distribution of Plasmodium vivax and Plasmodium falciparum malaria in China during 2005-2009. Global Moran's I statistics was used to detect a spatial distribution of local P. falciparum and P. vivax malaria at the county level. Spatial and space-time scan statistics were applied to detect spatial and spatiotemporal clusters, respectively. Both P. vivax and P. falciparum malaria showed spatial autocorrelation. The most likely spatial cluster of P. vivax was detected in northern Anhui province between 2005 and 2009, and western Yunnan province between 2010 and 2014. For P. falciparum, the clusters included several counties of western Yunnan province from 2005 to 2011, Guangxi from 2012 to 2013, and Anhui in 2014. The most likely space-time clusters of P. vivax malaria and P. falciparum malaria were detected in northern Anhui province and western Yunnan province, respectively, during 2005-2009. The spatial and space-time cluster analysis identified high-risk areas and periods for both P. vivax and P. falciparum malaria. Both malaria types showed significant spatial and spatiotemporal variations. Contrary to P. vivax, the high-risk areas for P. falciparum malaria shifted from the west to the east of China. Further studies are required to examine the spatial changes in risk of malaria transmission and identify the underlying causes of elevated risk in the high-risk areas.

  20. Case report of Plasmodium falciparum malaria presenting as wide complex tachycardia

    Institute of Scientific and Technical Information of China (English)

    Sunil Kumar; Diwan SK; Mahajan SN; Shilpa Bawankule; Chetan Mahure

    2011-01-01

    Malaria caused by Plasmodium falciparum is a multisystem disorder and may have diversity of clinical presentations. We are presenting a case report of patients of falciparum malaria who presented to us with palpitation and fever. On electrocardiogram he had wide complex tachycardia. This case reiterates the need to think of malaria in any case with symptoms of fever with chills, even with various unusual presentations like palpitation due to wide complex tachycardia, especially in endemic country like India.

  1. High incidence of Plasmodium vivax malaria in newly arrived Eritrean refugees in Sweden since May 2014.

    Science.gov (United States)

    Sonden, K; Castro, E; Törnnberg, L; Stenstrom, C; Tegnell, A; Farnert, A

    2014-09-04

    Since May 2014, an increase in Plasmodium vivax malaria has been observed in Sweden. As of 31 August 2014, 105 malaria cases have been reported in newly arrived Eritrean refugees, 84 of them P. vivax. The patients were mainly young men and reported migration through Ethiopia and/or Sudan. Severe anaemia and long symptom duration reflect inadequate healthcare during migration. Countries currently hosting Eritrean refugees need to consider P. vivax malaria in this group of migrants.

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

    Science.gov (United States)

    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.

  3. Differential induction of functional IgG using the Plasmodium falciparum placental malaria vaccine candidate VAR2CSA

    DEFF Research Database (Denmark)

    Pinto, Vera V; Ditlev, Sisse B; Jensen, Kamilla E

    2011-01-01

    In Plasmodium falciparum malaria endemic areas placental malaria (PM) is an important complication of malaria. The recurrence of malaria in primigravidae women irrespective of acquired protection during childhood is caused by the interaction between the parasite-expressed VAR2CSA antigen...

  4. Distribution of two species of malaria, Plasmodium falciparum and Plasmodium vivax, on Lombok Island, Indonesia.

    Science.gov (United States)

    Nagao, Yoshiro; Dachlan, Yoes Prijatna; Soedarto; Hidajati, Sri; Yotopranoto, Subagyo; Kusmartisnawati; Subekti, Sri; Ideham, Bariah; Tsuda, Yoshio; Kawabata, Masato; Takagi, Masahiro; Looareesuwan, Somchai

    2003-09-01

    Medical and entomological surveys were conducted to determine the risk factors of Plasmodium falciparum and P. vivax infections on Lombok Island, Indonesia, to find the risk factors and the main mosquito vectors for each malaria. Multivariate longitudinal analysis demonstrated two significant risk factors for infection with P. falciparum: disappearance of P. vivax parasitemia (p<0.001) and a specific study site (p<0.001). In contrast, younger age (p=0.024) and the interpolated virtual density of An. subpictus (p=0.041) were significantly associated with increased risk of infection with P. vivax. Thus, it seems that the distribution of P. vivax was determined largely by the presence of An. subpictus, whilst that of P. falciparum was influenced by antagonism with P. vivax. This result shows the importance of following-up treated P. vivax patients to identify recrudescence of P. falciparum in this area.

  5. Critical role of a K+ channel in Plasmodium berghei transmission revealed by targeted gene disruption

    DEFF Research Database (Denmark)

    Ellekvist, Peter; Maciel, Jorge; Mlambo, Godfree;

    2008-01-01

    through the mosquito vector remains unknown. We hypothesize that these two K(+) channels mediate the transport of K(+) in the parasites, and thus are important for parasite survival. To test this hypothesis, we identified the orthologue of one of the P. falciparum K(+) channels, PfKch1, in the rodent...... inhibition of the development of PbKch1-null parasites in Anopheles stephensi mosquitoes. In conclusion, these studies demonstrate that PbKch1 contributes to the transport of K(+) in P. berghei parasites and supports the growth of the parasites, in particular the development of oocysts in the mosquito midgut...

  6. Montanide, Poly I:C and nanoparticle based vaccines promote differential suppressor and effector cell expansion: a study of induction of CD8 T cells to a minimal Plasmodium berghei epitope

    Directory of Open Access Journals (Sweden)

    Kirsty Lee Wilson

    2015-02-01

    Full Text Available The development of practical and flexible vaccines to target liver stage malaria parasites would benefit from an ability to induce high levels of CD8 T cells to minimal peptide epitopes. Herein we compare different adjuvant and carrier systems in a murine model for induction of interferon gamma (IFN-γ producing CD8 T cells to the minimal immuno-dominant peptide epitope from the circumsporozoite protein (CSP of Plasmodium berghei, pb9 (SYIPSAEKI, referred to as KI. Two pro-inflammatory adjuvants, Montanide and Poly I:C, and a non-classical, non-inflammatory nanoparticle based carrier (polystyrene nanoparticles, PSNPs, were compared side-by-side for their ability to induce potentially protective CD8 T cell responses after two immunisations. KI in Montanide (Montanide + KI or covalently conjugated to PSNPs (PSNPs-KI induced such high responses, whereas adjuvanting with Poly I:C or PSNPs without conjugation was ineffective. This result was consistent with an observed induction of an immunosuppressed environment by Poly I:C in the draining lymph node (dLN 48 hours post injection, which was reflected by increased frequencies of myeloid derived suppressor cells (MDSC and a proportion of inflammation reactive regulatory T cells (Treg expressing the tumour necrosis factor receptor 2 (TNFR2, as well as decreased dendritic cell (DC maturation. The other inflammatory adjuvant, Montanide, also promoted proportional increases in the TNFR2+ Treg subpopulation, but not MDSCs, in the dLN. By contrast, injection with non-inflammatory PSNPs did not cause these changes. Induction of high CD8 T cell responses, using minimal peptide epitopes, can be achieved by non-inflammatory carrier nanoparticles, which in contrast to some conventional inflammatory adjuvants, do not expand either MDSCs or inflammation reactive Tregs at the site of priming.

  7. Identification and characterization of a liver stage-specific promoter region of the malaria parasite Plasmodium.

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    Susanne Helm

    Full Text Available During the blood meal of a Plasmodium-infected mosquito, 10 to 100 parasites are inoculated into the skin and a proportion of these migrate via the bloodstream to the liver where they infect hepatocytes. The Plasmodium liver stage, despite its clinical silence, represents a highly promising target for antimalarial drug and vaccine approaches. Successfully invaded parasites undergo a massive proliferation in hepatocytes, producing thousands of merozoites that are transported into a blood vessel to infect red blood cells. To successfully develop from the liver stage into infective merozoites, a tight regulation of gene expression is needed. Although this is a very interesting aspect in the biology of Plasmodium, little is known about gene regulation in Plasmodium parasites in general and in the liver stage in particular. We have functionally analyzed a novel promoter region of the rodent parasite Plasmodium berghei that is exclusively active during the liver stage of the parasite. To prove stage-specific activity of the promoter, GFP and luciferase reporter assays have been successfully established, allowing both qualitative and accurate quantitative analysis. To further characterize the promoter region, the transcription start site was mapped by rapid amplification of cDNA ends (5'-RACE. Using promoter truncation experiments and site-directed mutagenesis within potential transcription factor binding sites, we suggest that the minimal promoter contains more than one binding site for the recently identified parasite-specific ApiAP2 transcription factors. The identification of a liver stage-specific promoter in P. berghei confirms that the parasite is able to tightly regulate gene expression during its life cycle. The identified promoter region might now be used to study the biology of the Plasmodium liver stage, which has thus far proven problematic on a molecular level. Stage-specific expression of dominant-negative mutant proteins and

  8. Protection against Plasmodium falciparum malaria by PfSPZ Vaccine

    Science.gov (United States)

    Epstein, Judith E.; Paolino, Kristopher M.; Richie, Thomas L.; Sedegah, Martha; Singer, Alexandra; Ruben, Adam J.; Chakravarty, Sumana; Stafford, April; Ruck, Richard C.; Eappen, Abraham G.; Billingsley, Peter F.; Manoj, Anita; Moser, Kara; Nielsen, Robin; Tosh, Donna; Cicatelli, Susan; Ganeshan, Harini; Case, Jessica; Padilla, Debbie; Davidson, Silas; Saverino, Elizabeth; Murshedkar, Tooba; Gunasekera, Anusha; Twomey, Patrick S.; Reyes, Sharina; Moon, James E.; James, Eric R.; KC, Natasha; Li, Minglin; Abot, Esteban; Belmonte, Arnel; Hauns, Kevin; Belmonte, Maria; Huang, Jun; Vasquez, Carlos; Remich, Shon; Carrington, Mary; Abebe, Yonas; Tillman, Amy; Hickey, Bradley; Regules, Jason; Villasante, Eileen; Sim, B. Kim Lee

    2017-01-01

    BACKGROUND: A radiation-attenuated Plasmodium falciparum (Pf) sporozoite (SPZ) malaria vaccine, PfSPZ Vaccine, protected 6 of 6 subjects (100%) against homologous Pf (same strain as in the vaccine) controlled human malaria infection (CHMI) 3 weeks after 5 doses administered intravenously. The next step was to assess protective efficacy against heterologous Pf (different from Pf in the vaccine), after fewer doses, and at 24 weeks. METHODS: The trial assessed tolerability, safety, immunogenicity, and protective efficacy of direct venous inoculation (DVI) of 3 or 5 doses of PfSPZ Vaccine in non-immune subjects. RESULTS: Three weeks after final immunization, 5 doses of 2.7 × 105 PfSPZ protected 12 of 13 recipients (92.3% [95% CI: 48.0, 99.8]) against homologous CHMI and 4 of 5 (80.0% [10.4, 99.5]) against heterologous CHMI; 3 doses of 4.5 × 105 PfSPZ protected 13 of 15 (86.7% [35.9, 98.3]) against homologous CHMI. Twenty-four weeks after final immunization, the 5-dose regimen protected 7 of 10 (70.0% [17.3, 93.3]) against homologous and 1 of 10 (10.0% [–35.8, 45.6]) against heterologous CHMI; the 3-dose regimen protected 8 of 14 (57.1% [21.5, 76.6]) against homologous CHMI. All 22 controls developed Pf parasitemia. PfSPZ Vaccine was well tolerated, safe, and easy to administer. No antibody or T cell responses correlated with protection. CONCLUSIONS: We have demonstrated for the first time to our knowledge that PfSPZ Vaccine can protect against a 3-week heterologous CHMI in a limited group of malaria-naive adult subjects. A 3-dose regimen protected against both 3-week and 24-week homologous CHMI (87% and 57%, respectively) in this population. These results provide a foundation for developing an optimized immunization regimen for preventing malaria. TRIAL REGISTRATION: ClinicalTrials.gov NCT02215707. FUNDING: Support was provided through the US Army Medical Research and Development Command, Military Infectious Diseases Research Program, and the Naval Medical Research

  9. Is Plasmodium vivax malaria a severe malaria?: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Cho Naing

    2014-08-01

    Full Text Available Plasmodium vivax is one of the major species of malaria infecting humans. Although emphasis on P. falciparum is appropriate, the burden of vivax malaria should be given due attention. This study aimed to synthesize the evidence on severe malaria in P. vivax infection compared with that in P. falciparum infection.We searched relevant studies in electronic databases. The main outcomes required for inclusion in the review were mortality, severe malaria (SM and severe anaemia (SA. The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale. Overall, 26 studies were included. The main meta-analysis was restricted to the high quality studies. Eight studies (n = 27490 compared the incidence of SM between P. vivax infection and P. falciparum mono-infection; a comparable incidence was found in infants (OR: 0.45, 95% CI:0.04-5.68, I2:98%, under 5 year age group (OR: 2.06, 95% CI: 0.83-5.1, I2:83%, the 5-15 year-age group (OR: 0.6, 95% CI: 0.31-1.16, I2:81% and adults (OR: 0.83, 95% CI: 0.67-1.03, I2:25%. Six studies reported the incidences of SA in P. vivax infection and P. falciparum mono-infection; a comparable incidence of SA was found among infants (OR: 3.47, 95%:0.64-18.94, I2: 92%, the 5-15 year-age group (OR:0.71, 95% CI: 0.06-8.57, I2:82%. This was significantly lower in adults (OR:0.75, 95% CI: 0.62-0.92, I2:0%. Five studies (n = 71079 compared the mortality rate between vivax malaria and falciparum malaria. A lower rate of mortality was found in infants with vivax malaria (OR:0.61, 95% CI:0.5-0.76, I2:0%, while this was comparable in the 5-15 year- age group (OR: 0.43, 95% CI:0.06-2.91, I2:84% and the children of unspecified-age group (OR: 0.77, 95% CI:0.59-1.01, I2:0%.Overall, the present analysis identified that the incidence of SM in patients infected with P. vivax was considerable, indicating that P. vivax is a major cause of SM. Awareness of the clinical manifestations of vivax malaria should prompt

  10. Evidence that the Malaria Parasite Plasmodium falciparum Putative Rhoptry Protein 2 Localizes to the Golgi Apparatus throughout the Erythrocytic Cycle.

    Science.gov (United States)

    Hallée, Stéphanie; Richard, Dave

    2015-01-01

    Invasion of a red blood cell by Plasmodium falciparum merozoites is an essential step in the malaria lifecycle. Several of the proteins involved in this process are stored in the apical complex of the merozoite, a structure containing secretory organelles that are released at specific times during invasion. The molecular players involved in erythrocyte invasion thus represent potential key targets for both therapeutic and vaccine-based strategies to block parasite development. In our quest to identify and characterize new effectors of invasion, we investigated the P. falciparum homologue of a P. berghei protein putatively localized to the rhoptries, the Putative rhoptry protein 2 (PbPRP2). We show that in P. falciparum, the protein colocalizes extensively with the Golgi apparatus across the asexual erythrocytic cycle. Furthermore, imaging of merozoites caught at different times during invasion show that PfPRP2 is not secreted during the process instead staying associated with the Golgi apparatus. Our evidence therefore suggests that PfPRP2 is a Golgi protein and that it is likely not a direct effector in the process of merozoite invasion.

  11. Heterologous Protection against Malaria after Immunization with Plasmodium falciparum Sporozoites.

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    Remko Schats

    Full Text Available Sterile protection in >90% of volunteers against homologous Plasmodium falciparum infection has been achieved only using the controlled human malaria infection (CHMI model. This efficient model involves whole parasite immunizations under chloroquine prophylaxis (CPS-immunization, requiring only 30-45 mosquitoes bites infected with P. falciparum-sporozoites. Given the large diversity of P. falciparum parasites, it is essential to assess protection against heterologous parasite strains.In an open-label follow-up study, 16 volunteers previously CPS-immunized and challenged with P. falciparum NF54 (West-Africa in a dose de-escalation and challenge trial were re-challenged with clone NF135.C10 (Cambodia at 14 months after the last immunization (NCT01660854.Two out of thirteen NF54 protected volunteers previously fully protected against NF54 were also fully protected against NF135.C10, while 11/13 showed a delayed patency (median prepatent period of 10.5 days (range 9.0-15.5 versus 8.5 days in 5 malaria-naïve controls (p = 0.0005. Analysis of patency by qPCR indicated a 91 to >99% estimated reduction of liver parasite load in 7/11 partially protected subjects. Three volunteers previously not protected against NF54, were also not protected against NF135.C10.This study shows that CPS-immunization can induce heterologous protection for a period of more than one year, which is a further impetus for clinical development of whole parasite vaccines.Clinicaltrials.gov NCT01660854.

  12. Targeting Angiotensin II Type-1 Receptor (AT1R) Inhibits the Harmful Phenotype of Plasmodium-Specific CD8(+) T Cells during Blood-Stage Malaria.

    Science.gov (United States)

    Silva-Filho, João L; Caruso-Neves, Celso; Pinheiro, Ana A S

    2017-01-01

    CD8(+) T-cell response is critical in the pathogenesis of cerebral malaria during blood-stage. Our group and other have been shown that angiotensin II (Ang II) and its receptor AT1 (AT1R), a key effector axis of renin-angiotensin system (RAS), have immune regulatory effects on T cells. Previously, we showed that inhibition of AT1R signaling protects mice against the lethal disease induced by Plasmodium berghei ANKA infection However, most of the Ang II/AT1R actions were characterized by using only pharmacological approaches, the effects of which may not always be due to a specific receptor blockade. In addition, the mechanisms of action of the AT1R in inducing the pathogenic activity of Plasmodium-specific CD8(+) T cells during blood-stage were not determined. Here, we examined how angiotensin II/AT1R axis promotes the harmful response of Plasmodium-specific CD8(+) T-cell during blood-stage by using genetic and pharmacological approaches. We evaluated the response of wild-type (WT) and AT1R(-/-)Plasmodium-specific CD8(+) T cells in mice infected with a transgenic PbA lineage expressing ovalbumin; and in parallel infected mice receiving WT Plasmodium-specific CD8(+) T cells were treated with losartan (AT1R antagonist) or captopril (ACE inhibitor). Both, AT1R(-/-) OT-I cells and WT OT-I cells from losartan- or captopril-treated mice showed lower expansion, reduced IL-2 production and IL-2Rα expression, lower activation (lower expression of CD69, CD44 and CD160) and lower exhaustion profiles. AT1R(-/-) OT-I cells also exhibit lower expression of the integrin LFA-1 and the chemokine receptors CCR5 and CXCR3, known to play a key role in the development of cerebral malaria. Moreover, AT1R(-/-) OT-I cells produce lower amounts of IFN-γ and TNF-α and show lower degranulation upon restimulation. In conclusion, our results show the pivotal mechanisms of AT1R-induced harmful phenotype of Plasmodium-specific CD8(+) T cells during blood-stage malaria.

  13. Targeting Angiotensin II Type-1 Receptor (AT1R) Inhibits the Harmful Phenotype of Plasmodium-Specific CD8+ T Cells during Blood-Stage Malaria

    Science.gov (United States)

    Silva-Filho, João L.; Caruso-Neves, Celso; Pinheiro, Ana A. S.

    2017-01-01

    CD8+ T-cell response is critical in the pathogenesis of cerebral malaria during blood-stage. Our group and other have been shown that angiotensin II (Ang II) and its receptor AT1 (AT1R), a key effector axis of renin-angiotensin system (RAS), have immune regulatory effects on T cells. Previously, we showed that inhibition of AT1R signaling protects mice against the lethal disease induced by Plasmodium berghei ANKA infection However, most of the Ang II/AT1R actions were characterized by using only pharmacological approaches, the effects of which may not always be due to a specific receptor blockade. In addition, the mechanisms of action of the AT1R in inducing the pathogenic activity of Plasmodium-specific CD8+ T cells during blood-stage were not determined. Here, we examined how angiotensin II/AT1R axis promotes the harmful response of Plasmodium-specific CD8+ T-cell during blood-stage by using genetic and pharmacological approaches. We evaluated the response of wild-type (WT) and AT1R−/− Plasmodium-specific CD8+ T cells in mice infected with a transgenic PbA lineage expressing ovalbumin; and in parallel infected mice receiving WT Plasmodium-specific CD8+ T cells were treated with losartan (AT1R antagonist) or captopril (ACE inhibitor). Both, AT1R−/− OT-I cells and WT OT-I cells from losartan- or captopril-treated mice showed lower expansion, reduced IL-2 production and IL-2Rα expression, lower activation (lower expression of CD69, CD44 and CD160) and lower exhaustion profiles. AT1R−/− OT-I cells also exhibit lower expression of the integrin LFA-1 and the chemokine receptors CCR5 and CXCR3, known to play a key role in the development of cerebral malaria. Moreover, AT1R−/− OT-I cells produce lower amounts of IFN-γ and TNF-α and show lower degranulation upon restimulation. In conclusion, our results show the pivotal mechanisms of AT1R-induced harmful phenotype of Plasmodium-specific CD8+ T cells during blood-stage malaria. PMID:28261571

  14. 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.

  15. Targeting NAD+ metabolism in the human malaria parasite Plasmodium falciparum.

    Directory of Open Access Journals (Sweden)

    Jessica K O'Hara

    Full Text Available Nicotinamide adenine dinucleotide (NAD+ is an essential metabolite utilized as a redox cofactor and enzyme substrate in numerous cellular processes. Elevated NAD+ levels have been observed in red blood cells infected with the malaria parasite Plasmodium falciparum, but little is known regarding how the parasite generates NAD+. Here, we employed a mass spectrometry-based metabolomic approach to confirm that P. falciparum lacks the ability to synthesize NAD+ de novo and is reliant on the uptake of exogenous niacin. We characterized several enzymes in the NAD+ pathway and demonstrate cytoplasmic localization for all except the parasite nicotinamidase, which concentrates in the nucleus. One of these enzymes, the P. falciparum nicotinate mononucleotide adenylyltransferase (PfNMNAT, is essential for NAD+ metabolism and is highly diverged from the human homolog, but genetically similar to bacterial NMNATs. Our results demonstrate the enzymatic activity of PfNMNAT in vitro and demonstrate its ability to genetically complement the closely related Escherichia coli NMNAT. Due to the similarity of PfNMNAT to the bacterial enzyme, we tested a panel of previously identified bacterial NMNAT inhibitors and synthesized and screened twenty new derivatives, which demonstrate a range of potency against live parasite culture. These results highlight the importance of the parasite NAD+ metabolic pathway and provide both novel therapeutic targets and promising lead antimalarial compounds.

  16. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria

    Science.gov (United States)

    Ariey, Frédéric; Witkowski, Benoit; Amaratunga, Chanaki; Beghain, Johann; Langlois, Anne-Claire; Khim, Nimol; Kim, Saorin; Duru, Valentine; Bouchier, Christiane; Ma, Laurence; Lim, Pharath; Leang, Rithea; Duong, Socheat; Sreng, Sokunthea; Suon, Seila; Chuor, Char Meng; Bout, Denis Mey; Ménard, Sandie; Rogers, William O.; Genton, Blaise; Fandeur, Thierry; Miotto, Olivo; Ringwald, Pascal; Le Bras, Jacques; Berry, Antoine; Barale, Jean-Christophe; Fairhurst, Rick M.; Benoit-Vical, Françoise; Mercereau-Puijalon, Odile; Ménard, Didier

    2014-01-01

    Plasmodium falciparum resistance to artemisinin derivatives in southeast Asia threatens malaria control and elimination activities worldwide. To monitor the spread of artemisinin resistance, a molecular marker is urgently needed. Here, using whole-genome sequencing of an artemisinin-resistant parasite line from Africa and clinical parasite isolates from Cambodia, we associate mutations in the PF3D7_1343700 kelch propeller domain (`K13-propeller') with artemisinin resistance in vitro and in vivo. Mutant K13-propeller alleles cluster in Cambodian provinces where resistance is prevalent, and the increasing frequency of a dominant mutant K13-propeller allele correlates with the recent spread of resistance in western Cambodia. Strong correlations between the presence of a mutant allele, in vitro parasite survival rates and in vivo parasite clearance rates indicate that K13-propeller mutations are important determinants of artemisinin resistance. K13-propeller polymorphism constitutes a useful molecular marker for large-scale surveillance efforts to contain artemisinin resistance in the Greater Mekong Subregion and prevent its global spread.

  17. Targeting glycolysis in the malaria parasite Plasmodium falciparum.

    Science.gov (United States)

    van Niekerk, David D; Penkler, Gerald P; du Toit, Francois; Snoep, Jacky L

    2016-02-01

    Glycolysis is the main pathway for ATP production in the malaria parasite Plasmodium falciparum and essential for its survival. Following a sensitivity analysis of a detailed kinetic model for glycolysis in the parasite, the glucose transport reaction was identified as the step whose activity needed to be inhibited to the least extent to result in a 50% reduction in glycolytic flux. In a subsequent inhibitor titration with cytochalasin B, we confirmed the model analysis experimentally and measured a flux control coefficient of 0.3 for the glucose transporter. In addition to the glucose transporter, the glucokinase and phosphofructokinase had high flux control coefficients, while for the ATPase a small negative flux control coefficient was predicted. In a broader comparative analysis of glycolytic models, we identified a weakness in the P. falciparum pathway design with respect to stability towards perturbations in the ATP demand. The mathematical model described here has been submitted to the JWS Online Cellular Systems Modelling Database and can be accessed at http://jjj.bio.vu.nl/database/vanniekerk1. The SEEK-study including the experimental data set is available at DOI 10.15490/seek.1. 56 (http://dx.doi.org/10.15490/seek.1. 56). © 2015 FEBS.

  18. Haptoglobin 1-1 is associated with susceptibility to severe Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Quaye, I K; Ekuban, F A; Goka, B Q

    2000-01-01

    The haptoglobin (Hp) phenotypes were determined by polyacrylamide-gel electrophoresis in plasma samples obtained in 1997 from 113 Plasmodium falciparum malaria patients (aged 1-12 years) with strictly defined cerebral malaria, severe malarial anaemia, or uncomplicated malaria and 42 age...... the reverse was seen with respect to Hp2-1 and Hp2-2. Our data suggest that the Hp1-1 phenotype is associated with susceptibility to P. falciparum malaria in general, and to the development of severe disease in particular....

  19. Critical role of a K+ channel in Plasmodium berghei transmission revealed by targeted gene disruption

    DEFF Research Database (Denmark)

    Ellekvist, Peter; Maciel, Jorge; Mlambo, Godfree

    2008-01-01

    Regulated K(+) transport across the plasma membrane is of vital importance for the survival of most cells. Two K(+) channels have been identified in the Plasmodium falciparum genome; however, their functional significance during parasite life cycle in the vertebrate host and during transmission...

  20. A Review of Plasmodium coatneyi-Macaque Models of Severe Malaria.

    Science.gov (United States)

    Lombardini, E D; Gettayacamin, M; Turner, G D H; Brown, A E

    2015-11-01

    Malaria remains one of the most significant public health concerns in the world today. Approximately half the human population is at risk for infection, with children and pregnant women being most vulnerable. More than 90% of the total human malaria burden, which numbers in excess of 200 million annually, is due to Plasmodium falciparum. Lack of an effective vaccine and a dwindling stockpile of antimalarial drugs due to increased plasmodial resistance underscore the critical need for valid animal models. Plasmodium coatneyi was described in Southeast Asia 50 years ago. This plasmodium of nonhuman primates has been used sporadically as a model for severe malaria, as it mimics many of the pathophysiologic features of human disease. This review covers the reported macroscopic, microscopic, ultrastructural, and molecular pathology of P. coatneyi infection in macaques, specifically focusing on the rhesus macaque, as well as describing the critical needs still outstanding in the validation of this crucial model of human disease.

  1. Disruption of Plasmodium Sporozoite Transmission by Depletion of Sporozoite Invasion-Associated Protein 1▿ §

    OpenAIRE

    2009-01-01

    Accumulation of infectious Plasmodium sporozoites in Anopheles spp. salivary glands marks the final step of the complex development of the malaria parasite in the insect vector. Sporozoites are formed inside midgut-associated oocysts and actively egress into the mosquito hemocoel. Traversal of the salivary gland acinar cells correlates with the sporozoite's capacity to perform continuous gliding motility. Here, we characterized the cellular role of the Plasmodium berghei sporozoite invasion-a...

  2. 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...

  3. 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

  4. Contribution of Plasmodium knowlesi to Multispecies Human Malaria Infections in North Sumatera, Indonesia.

    Science.gov (United States)

    Lubis, Inke N D; Wijaya, Hendri; Lubis, Munar; Lubis, Chairuddin P; Divis, Paul C S; Beshir, Khalid B; Sutherland, Colin J

    2017-04-01

    As Indonesia works toward the goal of malaria elimination, information is lacking on malaria epidemiology from some western provinces. As a basis for studies of antimalarial efficacy, we set out to survey parasite carriage in 3 communities in North Sumatera Province. A combination of active and passive detection of infection was carried out among communities in Batubara, Langkat, and South Nias regencies. Finger-prick blood samples from consenting individuals of all ages provided blood films for microscopic examination and blood spots on filter paper. Plasmodium species were identified using nested polymerase chain reaction (PCR) of ribosomal RNA genes and a novel assay that amplifies a conserved sequence specific for the sicavar gene family of Plasmodium knowlesi. Of 3731 participants, 614 (16.5%) were positive for malaria parasites by microscopy. PCR detected parasite DNA in samples from 1169 individuals (31.3%). In total, 377 participants (11.8%) harbored P. knowlesi. Also present were Plasmodium vivax (14.3%), Plasmodium falciparum (10.5%) and Plasmodium malariae (3.4%). Amplification of sicavar is a specific and sensitive test for the presence of P. knowlesi DNA in humans. Subpatent and asymptomatic multispecies parasitemia is relatively common in North Sumatera, so PCR-based surveillance is required to support control and elimination activities.

  5. Thrombocytopenia in pregnant women with Plasmodium falciparum malaria in an area of unstable malaria transmission in eastern Sudan

    Directory of Open Access Journals (Sweden)

    Adam Mayyada B

    2012-08-01

    Full Text Available Abstract Background Blood platelet levels are being evaluated as predictive and prognostic indicators of the severity of malaria infections in humans. However, there are few studies on platelets and Plasmodium falciparum malaria during pregnancy. Methods A case–control study was conducted at Gadarif Hospital in Eastern Sudan, an area characterized by unstable malaria transmission. The aim of the study was to investigate thrombocytopenia in pregnant women with P. falciparum malaria (cases and healthy pregnant women (controls. Results The median (interquartile platelet counts were significantly lower in patients with malaria (N = 60 than in the controls (N = 60, 61, 000 (43,000–85,000 vs. 249,000 (204,000–300,000/μL, respectively, p P. falciparum malaria (N = 12 compared with those patients with uncomplicated P. falciparum malaria (N = 48, 68, 000 (33,000-88,000/μL vs. 61, 000 (45,000–85,000/μL, respectively, p = 0.8. While none of the control group had thrombocytopenia (platelet count p P. falciparum malaria, compared with the pregnant healthy control group, were at higher risk (OR = 10.1, 95% CI = 4.1–25.18; p  Conclusion P. falciparum malaria is associated with thrombocytopenia in pregnant women in this setting. More research is needed.

  6. Malária por Plasmodium falciparum: estudos proteômicos Plasmodium falciparum malaria: proteomic studies

    Directory of Open Access Journals (Sweden)

    Rodrigo Siqueira-Batista

    2012-12-01

    Full Text Available A despeito dos avanços no tratamento e das campanhas de prevenção e de controle da malária nos distintos continentes nos quais a moléstia grassa, a entidade mórbida permanece com significativa relevância no mundo contemporâneo. O Plasmodium falciparum é o grande responsável pela malária grave, caracterizada por distúrbios em diferentes órgãos e sistemas, com possibilidade de evolução ao óbito. Embora incipientes, os estudos proteômicos na malária têm trazido boas perspectivas para melhor compreensão dos aspectos biológicos do Plasmodium, assim como dos mecanismos fisiopatológicos, diagnósticos, terapêuticos e profiláticos da enfermidade. Desse modo, o objetivo do presente artigo é apresentar uma breve revisão das aplicações da análise proteômica na malária por P. falciparum.Despite advances in treatment and campaigns for prevention and control of malaria on the various continents where it is still rampant, this disease remains significantly relevant to the contemporary world. Plasmodium falciparum is the organism that is mainly responsible for severe malaria, which is characterized by disturbances in different organs and systems, with possibly fatal outcomes. Although incipient, proteomic studies of malaria have yielded favorable prospects for elucidating the biological aspects of Plasmodium as well as the pathophysiological, diagnostic, prophylactic, and therapeutic mechanisms of the disease. Thus, the aim of the present article is to present a brief review of the applications of proteomic analysis in P. falciparum malaria.

  7. Protease-associated cellular networks in malaria parasite Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    Lilburn Timothy G

    2011-12-01

    Full Text Available Abstract Background Malaria continues to be one of the most severe global infectious diseases, responsible for 1-2 million deaths yearly. The rapid evolution and spread of drug resistance in parasites has led to an urgent need for the development of novel antimalarial targets. Proteases are a group of enzymes that play essential roles in parasite growth and invasion. The possibility of designing specific inhibitors for proteases makes them promising drug targets. Previously, combining a comparative genomics approach and a machine learning approach, we identified the complement of proteases (degradome in the malaria parasite Plasmodium falciparum and its sibling species 123, providing a catalog of targets for functional characterization and rational inhibitor design. Network analysis represents another route to revealing the role of proteins in the biology of parasites and we use this approach here to expand our understanding of the systems involving the proteases of P. falciparum. Results We investigated the roles of proteases in the parasite life cycle by constructing a network using protein-protein association data from the STRING database 4, and analyzing these data, in conjunction with the data from protein-protein interaction assays using the yeast 2-hybrid (Y2H system 5, blood stage microarray experiments 678, proteomics 9101112, literature text mining, and sequence homology analysis. Seventy-seven (77 out of 124 predicted proteases were associated with at least one other protein, constituting 2,431 protein-protein interactions (PPIs. These proteases appear to play diverse roles in metabolism, cell cycle regulation, invasion and infection. Their degrees of connectivity (i.e., connections to other proteins, range from one to 143. The largest protease-associated sub-network is the ubiquitin-proteasome system which is crucial for protein recycling and stress response. Proteases are also implicated in heat shock response, signal peptide

  8. Experimental investigation of avian malaria parasites (Plasmodium, Haemosporida): linkage of traditional and molecular data

    OpenAIRE

    2009-01-01

    Avian malaria parasites are responsible for severe diseases in some domestic and wild birds. These parasites are cosmopolitan in distribution; they are widespread in Europe, including the Baltic region. A peculiarity of current studies of avian Plasmodium species is that information about ecology, distribution, prevalence and other aspects of their biology has been accumulated using free-living birds. To elucidate the significance of malaria infections and their impact on host fitness, behavi...

  9. Lipid peroxidation and antioxidant enzymes activity in Plasmodium vivax malaria patients evolving with cholestatic jaundice

    OpenAIRE

    Fabbri, Camila; de Cássia Mascarenhas-Netto, Rita; Lalwani, Pritesh; Melo, Gisely C; Magalhães, Belisa ML; Alexandre, Márcia AA; Lacerda,Marcus VG; Emerson S. Lima

    2013-01-01

    Background Plasmodium vivax infection has been considered a benign and self-limiting disease, however, recent studies highlight the association between vivax malaria and life-threatening manifestations. Increase in reactive oxygen species has already been described in vivax malaria, as a result of the increased metabolic rate triggered by the multiplying parasite, and large quantities of toxic redox-active byproducts generated. The present study aimed to study the oxidative stress responses i...

  10. International funding for malaria control in relation to populations at risk of stable Plasmodium falciparum transmission.

    OpenAIRE

    Snow, Robert W; Guerra, Carlos A; Mutheu, Juliette J; Simon I Hay

    2008-01-01

    Editors' Summary Background. Malaria is one of the most common infectious diseases in the world and one of the greatest global public health problems. The Plasmodium falciparum parasite causes approximately 500 million cases each year and over one million deaths. More than 40% of the world's population is at risk of malaria. The Millennium Development Goals (MDGs), established by the United Nations in 2000, include a target in Goal 6: ?to have halted by 2015 and begun to reverse the incidence...

  11. Plasmodium malariae Infection Associated with a High Burden of Anemia: A Hospital-Based Surveillance Study.

    Directory of Open Access Journals (Sweden)

    Siobhan Langford

    2015-12-01

    Full Text Available Plasmodium malariae is a slow-growing parasite with a wide geographic distribution. Although generally regarded as a benign cause of malaria, it has been associated with nephrotic syndrome, particularly in young children, and can persist in the host for years. Morbidity associated with P. malariae infection has received relatively little attention, and the risk of P. malariae-associated nephrotic syndrome is unknown.We used data from a very large hospital-based surveillance system incorporating information on clinical diagnoses, blood cell parameters and treatment to describe the demographic distribution, morbidity and mortality associated with P. malariae infection in southern Papua, Indonesia. Between April 2004 and December 2013 there were 1,054,674 patient presentations to Mitra Masyarakat Hospital of which 196,380 (18.6% were associated with malaria and 5,097 were with P. malariae infection (constituting 2.6% of all malaria cases. The proportion of malaria cases attributable to P. malariae increased with age from 0.9% for patients under one year old to 3.1% for patients older than 15 years. Overall, 8.5% of patients with P. malariae infection required admission to hospital and the median length of stay for these patients was 2.5 days (Interquartile Range: 2.0-4.0 days. Patients with P. malariae infection had a lower mean hemoglobin concentration (9.0 g/dL than patients with P. falciparum (9.5 g/dL, P. vivax (9.6g/dL and mixed species infections (9.3g/dL. There were four cases of nephrotic syndrome recorded in patients with P. malariae infection, three of which were in children younger than 5 years old, giving a risk in this age group of 0.47% (95% Confidence Interval; 0.10% to 1.4%. Overall, 2.4% (n = 16 of patients hospitalized with P. malariae infection subsequently died in hospital, similar to the proportions for the other endemic Plasmodium species (range: 0% for P. ovale to 1.6% for P. falciparum.Plasmodium malariae infection is

  12. 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...

  13. Evaluation of a rapid whole blood immunochromatographic assay for the diagnosis of Plasmodium falciparum and Plasmodium vivax malaria.

    Science.gov (United States)

    Fernando, S D; Karunaweera, N D; Fernando, W P

    2004-03-01

    Microscopic examination of blood smears is the 'gold standard' for malaria diagnosis, but is labour intensive and requires skilled operators. Plasmodium vivax malaria accounts for up to 70% of infections in Sri Lanka. The objective of this study was to determine the effectiveness of an immunochromatographic test which can detect both the species of Plasmodium, P. vivax and P. falciparum, present in Sri Lanka. Prospective study from May 2001 to March 2002. All persons above 5 years of age who presented to the Malaria Research Station, Kataragama or the Anti-malaria Clinic, Kurunegala, with a history of fever were recruited to the study. Thick and thin blood smears were examined for malarial parasites. The rapid diagnostic test (RDT), ICT Malaria P.f/P.v (AMRAD ICT, Australia) was performed simultaneously by an independent investigator. The severity of clinical disease of all patients was evaluated. The study sample comprised 328 individuals of whom 126 (38%) were infected, 102 with P. vivax (31.1%) and 24 with P. falciparum (7.3%). The RDT was found to be highly sensitive (100%) and specific (100%) for the diagnosis of P. falciparum when compared with field microscopy. The sensitivity for the diagnosis of P. vivax malaria was only 70%. When P. vivax parasitaemia was greater than 5000 parasites/microL the RDT was 96.2% sensitive. A significant association was noted between the band intensity on the dipstick and both peripheral blood parasitaemia (p ICT Malaria P.f/P.v test can be used in Sri Lanka in the absence of microscopists.

  14. Effects of Aging on Parasite Biomass, Inflammation, Endothelial Activation, Microvascular Dysfunction and Disease Severity in Plasmodium knowlesi and Plasmodium falciparum Malaria.

    Science.gov (United States)

    Barber, Bridget E; Grigg, Matthew J; William, Timothy; Piera, Kim A; Boyle, Michelle J; Yeo, Tsin W; Anstey, Nicholas M

    2017-06-15

    In populations pauci-immune to malaria, risk of severe malaria increases with age. This is particularly apparent in Plasmodium knowlesi malaria. However, pathophysiological mechanisms underlying knowlesi malaria, and of the age-related increase in risk of severe malaria in general, are poorly understood. In Malaysian patients aged ≥12 years with severe (n = 47) and nonsevere (n = 99) knowlesi malaria, severe (n = 21) and nonsevere (n = 109) falciparum malaria, and healthy controls (n = 50), we measured parasite biomass, systemic inflammation (interleukin 6 [IL-6]), endothelial activation (angiopoietin-2), and microvascular function, and evaluated the effects of age. Plasmodium knowlesi parasitemia correlated with age (Spearman's correlation coefficient [rs] = 0.36; P falciparum malaria, angiopoietin-2 increased with age, independent of parasite biomass (histidine-rich protein 2 [HRP2]). Independent risk factors for severe malaria included parasitemia and angiopoietin-2 in knowlesi malaria, and HRP2, angiopoietin-2, and microvascular dysfunction in falciparum malaria. Parasite biomass, endothelial activation, and microvascular dysfunction are associated with severe disease in knowlesi malaria and likely contribute to pathogenesis. The association of each of these processes with aging may account for the greater severity of malaria observed in older adults in low-endemic regions.

  15. Artesunate plus pyronaridine for treating uncomplicated Plasmodium falciparum malaria

    Science.gov (United States)

    Bukirwa, Hasifa; Unnikrishnan, B; Kramer, Christine V; Sinclair, David; Nair, Suma; Tharyan, Prathap

    2014-01-01

    Background The World Health Organization (WHO) recommends that people with uncomplicated Plasmodium falciparum malaria are treated using Artemisinin-based Combination Therapy (ACT). ACT combines three-days of a short-acting artemisinin derivative with a longer-acting antimalarial which has a different mode of action. Pyronaridine has been reported as an effective antimalarial over two decades of use in parts of Asia, and is currently being evaluated as a partner drug for artesunate. Objectives To evaluate the efficacy and safety of artesunate-pyronaridine compared to alternative ACTs for treating people with uncomplicated P. falciparum malaria. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library; MEDLINE; EMBASE; LILACS; ClinicalTrials.gov; the metaRegister of Controlled Trials (mRCT); and the WHO International Clinical Trials Search Portal up to 16 January 2014. We searched reference lists and conference abstracts, and contacted experts for information about ongoing and unpublished trials. Selection criteria Randomized controlled trials of artesunate-pyronaridine versus other ACTs in adults and children with uncomplicated P. falciparum malaria. For the safety analysis, we also included adverse events data from trials comparing any treatment regimen containing pyronaridine with regimens not containing pyronaridine. Data collection and analysis Two authors independently assessed trial eligibility and risk of bias, and extracted data. We combined dichotomous data using risk ratios (RR) and continuous data using mean differences (MD), and presented all results with a 95% confidence interval (CI). We used the GRADE approach to assess the quality of evidence. Main results We included six randomized controlled trials enrolling 3718 children and adults. Artesunate-pyronaridine versus artemether-lumefantrine In two multicentre trials, enrolling

  16. Análisis proteómico de Plasmodium, el agente causal de la malaria Proteomic analysis of Plasmodium, the causal agent of Malaria

    Directory of Open Access Journals (Sweden)

    Ivone Castro R

    2009-01-01

    Full Text Available Los plasmodios son protozoarios cuyo complejo ciclo de vida se lleva a cabo en dos hospederos, el vertebrado y el mosquito. La infección de los seres humanos produce la enfermedad conocida como malaria. La secuenciación del genoma de Plasmodium falciparum y el desarrollo de la proteómica han permitido un gran avance en el conocimiento de la biología de este letal parásito. La presente revisión se centra en describir los logros recientes en el estudio del proteoma de Plasmodium falciparum y algunas de las implicaciones en la búsqueda de nuevos fármacos antimaláricos, así como en la generación de vacunas para el control de la enfermedad.Plasmodia are protozoa whose complex life cycle takes place in two different hosts, the vertebrate and the mosquito. The human infection produces the malaria disease. The genome sequence of Plasmodium falciparum and the proteomic tools have enabled a huge advance in knowledge of the biology of this parasite. This review will focus on the recent advances in proteomic studies of Plasmodium falciparum and some implications for the search of new antimalarial drugs as well as vaccines for the control of the disease.

  17. Transportproteiner som drug-targets hos Plasmodium falciparum. Nye perspektiver i behandlingen af malaria

    DEFF Research Database (Denmark)

    Ellekvist, Peter; Colding, Hanne

    2006-01-01

    The malaria parasite, Plasmodium falciparum, infects and replicates in human erythrocytes. Through the use of substrate-specific transport proteins, P. falciparum takes up nutrients from the erythrocyte's cytoplasm. The sequencing and publishing of the P. falciparum genome have made it possible...

  18. Differences in gene transcriptomic pattern of Plasmodium falciparum in children with cerebral malaria and asymptomatic carriers

    DEFF Research Database (Denmark)

    Almelli, Talleh; Nuel, Grégory; Bischoff, Emmanuel

    2014-01-01

    , transcriptional factor proteins, proteins implicated in protein transport, as well as Plasmodium conserved and hypothetical proteins. Interestingly, UPs A1, A2, A3 and UPs B1 of var genes were predominantly found in cerebral malaria-associated isolates and those containing architectural domains of DC4, DC5, DC13...

  19. How malaria modulates memory: activation and dysregulation of B cells in Plasmodium infection

    NARCIS (Netherlands)

    Scholzen, A.; Sauerwein, R.W.

    2013-01-01

    Humoral immune responses play a major role in naturally acquired immunity to malaria, but are slow to develop and ineffectively maintained. Although this may be partially due to the complex nature of Plasmodium parasites and the high degree of antigenic variation, there is evidence that the parasite

  20. Human Plasmodium knowlesi infection detected by rapid diagnostic tests for malaria

    NARCIS (Netherlands)

    J.J. van Hellemond (Jaap); M. Rutten (Martine); R. Koelewijn (Rob); A.M. Zeeman (Anne Marie); J. Verweij (Jaap); P.J. Wismans (Pieter); C.H. Kocken (Clemens); P.J.J. van Genderen (Perry)

    2009-01-01

    textabstractWe describe a PCR-confirmed case of Plasmodium knowlesi infection with a high parasitemia level and clinical signs of severe malaria in a migrant worker from Malaysian Borneo in the Netherlands. Investigations showed that commercially available rapid antigen tests for detection of human

  1. The efficacy of artemether in the treatment of Plasmodium falciparum malaria in Sudan

    DEFF Research Database (Denmark)

    Elhassan, I M; Satti, G H; Ali, A E

    1994-01-01

    The efficacy of artemether (a qinghaosu derivative) administered intramuscularly for the treatment of Plasmodium falciparum malaria was compared to quinine in an open randomized trial including 54 patients in eastern Sudan, where chloroquine resistance is common. The artemether treatment (5 d...

  2. Cytokine production and apoptosis among T cells from patients under treatment for Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Kemp, K; Akanmori, B D; Adabayeri, V

    2002-01-01

    Available evidence suggests that Plasmodium falciparum malaria causes activation and reallocation of T cells, and that these in vivo primed cells re-emerge into the periphery following drug therapy. Here we have examined the cytokine production capacity and susceptibility to programmed cell death...

  3. Increased levels of soluble CD30 in plasma of patients with Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

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

    2002-01-01

    Levels of soluble CD30 (sCD30) in serum were elevated in patients with Plasmodium falciparum malaria but showed decline following treatment. The levels of sCD30 in serum were correlated significantly with the expression of gamma interferon by peripheral T cells. These data suggest that CD30...

  4. Drug resistance to sulphadoxine-pyrimethamine in Plasmodium falciparum malaria in Mlimba, Tanzania

    NARCIS (Netherlands)

    Mbugi, E.V.; Mutayoba, B.M.; Malisa, A.L.; Balthazary, S.T.; Nyambo, T.B.; Mshinda, H.

    2006-01-01

    Background - Sulphadoxine-pyrimethamine (SP) has been and is currently used for treatment of uncomplicated Plasmodium falciparum malaria in many African countries. Nevertheless, the response of parasites to SP treatment has shown significant variation between individuals. Methods - The genes for dih

  5. Anti-Plasmodium immunoglobulin E in children of Urabá (Colombia according to the presence of malaria = Inmunoglobulina E anti-Plasmodium en niños de Urabá (Colombia según la presencia de malaria

    Directory of Open Access Journals (Sweden)

    Jaime Carmona-Fonseca

    2013-10-01

    Full Text Available Problem: We are not aware of studies in Colombia on levels of specific IgE in children without malaria and only one is available in children with uncomplicated malaria. Objective: To measure anti-Plasmodium IgE in children with or without malaria according to sex, nutritional status, and the presence of intestinal helminthes, and the relations with hematologic variables. Methodology: anti-Plasmodium IgE was measured in 335 children without malaria and in 125 with uncomplicated malaria (P. vivax: 116; P. falciparum: 9. Measurement was done with the ELISA technique, with a crude antigen extract of P. falciparum FCB-2 strain. We used Sigma`s conjugated anti-anti-IgE A3525. IgE was measured and expressed as optical density (absorbance. Results: Anti-Plasmodium IgE in children without malaria was 0.808 ± 0.508 (cutoff point used to define high level: 0.584 and 1.968 ± 1.237 in children with malaria (p = 0.000000. Anti-Plasmodium IgE levels showed no significant difference according to plasmodial species but there was significant difference by sex and nutritional status. In children without malaria, the level of anti-Plasmodium IgE was higher in those with the presence of roundworm, whipworm and hookworm, but the difference was significant only for roundworms. The level of anti-Plasmodium IgE showed significant positive linear correlation with the number of eggs of Ascaris and whipworm per gram of stool. Conclusions: In Urabá, children with or without malaria have elevated levels of anti-Plasmodium IgE, that are higher in women and in those affected by malaria.

  6. Complement Activation Correlates With Disease Severity and Contributes to Cytokine Responses in Plasmodium falciparum Malaria.

    Science.gov (United States)

    Berg, Aase; Otterdal, Kari; Patel, Sam; Gonca, Miguel; David, Catarina; Dalen, Ingvild; Nymo, Stig; Nilsson, Margareta; Nordling, Sofia; Magnusson, Peetra U; Ueland, Thor; Prato, Mauro; Giribaldi, Giuliana; Mollnes, Tom Eirik; Aukrust, Pål; Langeland, Nina; Nilsson, Per H

    2015-12-01

    The impact of complement activation and its possible relation to cytokine responses during malaria pathology was investigated in plasma samples from patients with confirmed Plasmodium falciparum malaria and in human whole-blood specimens stimulated with malaria-relevant agents ex vivo. Complement was significantly activated in the malaria cohort, compared with healthy controls, and was positively correlated with disease severity and with certain cytokines, in particular interleukin 8 (IL-8)/CXCL8. This was confirmed in ex vivo-stimulated blood specimens, in which complement inhibition significantly reduced IL-8/CXCL8 release. P. falciparum malaria is associated with systemic complement activation and complement-dependent release of inflammatory cytokines, of which IL-8/CXCL8 is particularly prominent. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  7. Predictors of Plasmodium falciparum malaria incidence in Chano Mille, South Ethiopia: a longitudinal study.

    Science.gov (United States)

    Loha, Eskindir; Lindtjørn, Bernt

    2012-09-01

    We assessed potential effects of local meteorological and environmental conditions, indoor residual spraying with insecticides, insecticide-treated nets (ITNs) use at individual and community levels, and individual factors on Plasmodium falciparum malaria incidence in a village in south Ethiopia. A cohort of 8,121 people was followed for 101 weeks with active and passive surveillance. Among 317 microscopically confirmed P. falciparum malaria episodes, 29.3% occurred among temporary residents. The incidence density was 3.6/10,000 person-weeks of observation. We observed higher malaria incidence among males, children 5-14 years of age, ITNs non-users, the poor, and people who lived closer to vector breeding places. Rainfall increased and indoor residual spraying with Deltamethrin reduced falciparum incidence. Although ITNs prevented falciparum malaria for the users, we did not find that free mass ITNs distribution reduced falciparum malaria on a village level.

  8. Distinct patterns of cytokine regulation in discrete clinical forms of Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Akanmori, B D; Kurtzhals, J A; Goka, B Q;

    2000-01-01

    The pathogenesis of two of the most severe complications of Plasmodium falciparum malaria, cerebral malaria (CM) and severe malarial anaemia (SA) both appear to involve dysregulation of the immune system. We have measured plasma levels of TNF and its two receptors in Ghanaian children with strictly...... defined cerebral malaria (CM), severe malarial anaemia (SA), or uncomplicated malaria (UM) in two independent studies in an area of seasonal, hyperendemic transmission of P. falciparum. Levels of TNF, soluble TNF receptor 1 (sTNF-R1) and 2 (sTNF-R2) were found to be significantly higher in CM than...... in the other clinical categories of P. falciparum malaria patients. Levels of both receptors depended on clinical category, whereas only sTNF-R1 levels were significantly dependent on parasitemia. Detailed analysis of the interrelationship between these variables resolved this pattern further, and identified...

  9. Plasmodium genome in blood donors at risk for malaria after several years of residence in Italy.

    Science.gov (United States)

    Assennato, Sonny Michael; Berzuini, Alessandra; Foglieni, Barbara; Spreafico, Marta; Allain, Jean-Pierre; Prati, Daniele

    2014-10-01

    At present, the main risk of transfusion-transmitted malaria (TTM) in nonendemic countries is chronic, asymptomatic immigrants from malaria-endemic areas. Semi-immune donors may carry undetected parasitemia. This study examines Plasmodium infection in at-risk blood donors in Northern Italy. Plasma samples from 97 candidate donors and 80 controls were tested for malarial antibodies using a commercial enzyme immunoassay. The conserved 18S rRNA and the mitochondrial genes of Plasmodium were amplified to detect and quantify parasite genomes (copies/mL). Plasmodium species were identified with a species-specific nested polymerase chain reaction. Parasitemic samples were further tested by amplification of polymorphic repetitive regions in MSP-1 Block 2, MSP-2 Block 3, and glutamate-rich protein (GLURP) confirmed by sequencing. Three of 83 seropositive (3.6%) and one of 14 seronegative at-risk candidate donors carried Plasmodium genome (4 × 10(3) -8.5 × 10(4) copies/mL): two P. falciparum, one P. malariae (seronegative sample), and one coinfection with P. malariae and P. ovale. Alleles of MSP-1 (MAD20 and K1), MSP-2 (3D7 and FC27), and GLURP were amplified from Sample 261. In Sample 282 only one allele in MSP-2 (FC27) and GLURP was amplified. No alleles were detected in Samples 283 and 331. Immigrants from endemic countries might carry infectious Plasmodium after 2 to 5 years of continuous residence in Italy. Serologic screening may miss donors carrying P. malariae. Permanent exclusion or screening for both antibodies and genome are needed to prevent TTM. © 2014 AABB.

  10. Targeting the hypnozoite reservoir of Plasmodium vivax: the hidden obstacle to malaria elimination.

    Science.gov (United States)

    Wells, Timothy N C; Burrows, Jeremy N; Baird, J Kevin

    2010-03-01

    Plasmodium vivax is the major species of malaria parasite outside Africa. It is especially problematic in that the infection can relapse in the absence of mosquitoes by activation of dormant hypnozoites in the liver. Medicines that target the erythrocytic stages of Plasmodium falciparum are also active against P. vivax, except where these have been compromised by resistance. However, the only clinical therapy against relapse of vivax malaria is the 8-aminoquinoline, primaquine. This molecule has the drawback of causing haemolysis in genetically sensitive patients and requires 14 days of treatment. New, safer and more-easily administered drugs are urgently needed, and this is a crucial gap in the broader malaria-elimination agenda. New developments in cell biology are starting to open ways to the next generation of drugs against hypnozoites. This search is urgent, given the time needed to develop a new medication.

  11. Dihydroartemisinin-piperaquine for treating uncomplicated Plasmodium falciparum malaria

    Science.gov (United States)

    Zani, Babalwa; Gathu, Michael; Donegan, Sarah; Olliaro, Piero L; Sinclair, David

    2014-01-01

    Background The World Health Organization (WHO) recommends Artemisinin-based Combination Therapy (ACT) for treating uncomplicated Plasmodium falciparum malaria. This review aims to assist the decision-making of malaria control programmes by providing an overview of the relative effects of dihydroartemisinin-piperaquine (DHA-P) versus other recommended ACTs. Objectives To evaluate the effectiveness and safety of DHA-P compared to other ACTs for treating uncomplicated P. falciparum malaria in adults and children. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL) published in The Cochrane Library; MEDLINE; EMBASE; LILACS, and the metaRegister of Controlled Trials (mRCT) up to July 2013. Selection criteria Randomized controlled trials comparing a three-day course of DHA-P to a three-day course of an alternative WHO recommended ACT in uncomplicated P. falciparum malaria. Data collection and analysis Two authors independently assessed trials for eligibility and risk of bias, and extracted data. We analysed primary outcomes in line with the WHO 'Protocol for assessing and monitoring antimalarial drug efficacy’ and compared drugs using risk ratios (RR) and 95% confidence intervals (CI). Secondary outcomes were effects on gametocytes, haemoglobin, and adverse events. We assessed the quality of evidence using the GRADE approach. Main results We included 27 trials, enrolling 16,382 adults and children, and conducted between 2002 and 2010. Most trials excluded infants aged less than six months and pregnant women. DHA-P versus artemether-lumefantrine In Africa, over 28 days follow-up, DHA-P is superior to artemether-lumefantrine at preventing further parasitaemia (PCR-unadjusted treatment failure: RR 0.34, 95% CI 0.30 to 0.39, nine trials, 6200 participants, high quality evidence), and although PCR-adjusted treatment failure was below 5% for both ACTs, it was consistently lower

  12. Proteomic identification of host and parasite biomarkers in saliva from patients with uncomplicated Plasmodium falciparum malaria

    Directory of Open Access Journals (Sweden)

    Huang Honglei

    2012-05-01

    Full Text Available Abstract Background Malaria cases attributed to Plasmodium falciparum account for approximately 600,000 deaths yearly, mainly in African children. The gold standard method to diagnose malaria requires the visualization of the parasite in blood. The role of non-invasive diagnostic methods to diagnose malaria remains unclear. Methods A protocol was optimized to deplete highly abundant proteins from saliva to improve the dynamic range of the proteins identified and assess their suitability as candidate biomarkers of malaria infection. A starch-based amylase depletion strategy was used in combination with four different lectins to deplete glycoproteins (Concanavalin A and Aleuria aurantia for N-linked glycoproteins; jacalin and peanut agglutinin for O-linked glycoproteins. A proteomic analysis of depleted saliva samples was performed in 17 children with fever and a positive–malaria slide and compared with that of 17 malaria-negative children with fever. Results The proteomic signature of malaria-positive patients revealed a strong up-regulation of erythrocyte-derived and inflammatory proteins. Three P. falciparum proteins, PFL0480w, PF08_0054 and PFI0875w, were identified in malaria patients and not in controls. Aleuria aurantia and jacalin showed the best results for parasite protein identification. Conclusions This study shows that saliva is a suitable clinical specimen for biomarker discovery. Parasite proteins and several potential biomarkers were identified in patients with malaria but not in patients with other causes of fever. The diagnostic performance of these markers should be addressed prospectively.

  13. Plasmodium spp.: an experimental study on vertebrate host susceptibility to avian malaria.

    Science.gov (United States)

    Dimitrov, Dimitar; Palinauskas, Vaidas; Iezhova, Tatjana A; Bernotienė, Rasa; Ilgūnas, Mikas; Bukauskaitė, Dovile; Zehtindjiev, Pavel; Ilieva, Mihaela; Shapoval, Anatoly P; Bolshakov, Casimir V; Markovets, Mikhail Yu; Bensch, Staffan; Valkiūnas, Gediminas

    2015-01-01

    The interest in experimental studies on avian malaria caused by Plasmodium species has increased recently due to the need of direct information about host-parasite interactions. Numerous important issues (host susceptibility, development of infection, the resistance and tolerance to avian malaria) can be answered using experimental infections. However, specificity of genetically different lineages of malaria parasites and their isolates is largely unknown. This study reviews recent experimental studies and offers additional data about susceptibility of birds to several widespread cytochrome b (cyt b) lineages of Plasmodium species belonging to four subgenera. We exposed two domesticated avian hosts (canaries Serinus canaria and ducklings Anas platyrhynchos) and also 16 species of common wild European birds to malaria infections by intramuscular injection of infected blood and then tested them by microscopic examination and PCR-based methods. Our study confirms former field and experimental observations about low specificity and wide host-range of Plasmodium relictum (lineages SGS1 and GRW11) and P. circumflexum (lineage TURDUS1) belonging to the subgenera Haemamoeba and Giovannolaia, respectively. However, the specificity of different lineages and isolates of the same parasite lineage differed between species of exposed hosts. Several tested Novyella lineages were species specific, with a few cases of successful development in experimentally exposed birds. The majority of reported cases of mortality and high parasitaemia were observed during parasite co-infections. Canaries were susceptible mainly for the species of Haemamoeba and Giovannolaia, but were refractory to the majority of Novyella isolates. Ducklings were susceptible to three malaria infections (SGS1, TURDUS1 and COLL4), but parasitaemia was light (<0.01%) and transient in all exposed birds. This study provides novel information about susceptibility of avian hosts to a wide array of malaria parasite

  14. 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

  15. The emerging of the fifth malaria parasite (Plasmodium knowlesi: a public health concern?

    Directory of Open Access Journals (Sweden)

    Sergio Sabbatani

    Full Text Available After examining the most recent scientific evidences, which assessed the role of some malaria plasmodia that have monkeys as natural reservoirs, the authors focus their attention on Plasmodium knowlesi. The infective foci attributable to this last Plasmodium species have been identified during the last decade in Malaysia, in particular in the states of Sarawak and Sabah (Malaysian Borneo, and in the Pahang region (peninsular Malaysia. The significant relevance of molecular biology assays (polymerase chain reaction, or PCR, performed with specific primers for P. knowlesi, is underlined, since the traditional microscopic examination does not offer distinguishing features, especially when the differential diagnosis with Plasmodium malariae is of concern. Furthermore, Plasmodium knowlesi disease may be responsible of fatal cases, since its clinical presentation and course is more severe compared with those caused by P. malariae, paralleling a more elevated parasitemia. The most effective mosquito vector is represented by Anopheles latens; this mosquito is a parasite of both humans and monkeys. Among primates, the natural hosts are Macaca fascicularis, M. nemestina, M. inus, and Saimiri scirea. When remarking the possible severe evolution of P. knowlesi malaria, we underline the importance of an early recognition and a timely management, especially in patients who have their first onset in Western Hospitals, after journeys in Southeast Asian countries, and eventually participated in trekking excursions in the tropical forest. When malaria-like signs and symptoms are present, a timely diagnosis and treatment become crucial. In the light of its emerging epidemiological features, P. knowlesi may be added to the reknown human malaria parasites, whith includes P. vivax, P. ovale, P. malariae, and P. falciparum, as the fifth potential ethiologic agent of human malaria. Over the next few years, it will be mandatory to support an adequate surveillance and

  16. Adaptation of the genetically tractable malaria pathogen Plasmodium knowlesi to continuous culture in human erythrocytes

    KAUST Repository

    Moon, Robert

    2012-12-24

    Research into the aetiological agent of the most widespread form of severe malaria, Plasmodium falciparum, has benefitted enormously from the ability to culture and genetically manipulate blood-stage forms of the parasite in vitro. However, most malaria outside Africa is caused by a distinct Plasmodium species, Plasmodium vivax, and it has become increasingly apparent that zoonotic infection by the closely related simian parasite Plasmodium knowlesi is a frequent cause of life-threatening malaria in regions of southeast Asia. Neither of these important malarial species can be cultured in human cells in vitro, requiring access to primates with the associated ethical and practical constraints. We report the successful adaptation of P. knowlesi to continuous culture in human erythrocytes. Human-adapted P. knowlesi clones maintain their capacity to replicate in monkey erythrocytes and can be genetically modified with unprecedented efficiency, providing an important and unique model for studying conserved aspects of malarial biology as well as species-specific features of an emerging pathogen.

  17. Plasmodium activates the innate immune response of Anopheles gambiae mosquitoes.

    OpenAIRE

    Richman, A M; Dimopoulos, G; Seeley, D; Kafatos, F C

    1997-01-01

    Innate immune-related gene expression in the major disease vector mosquito Anopheles gambiae has been analyzed following infection by the malaria parasite, Plasmodium berghei. Substantially increased levels of mRNAs encoding the antibacterial peptide defensin and a putative Gram-negative bacteria-binding protein (GNBP) are observed 20-30 h after ingestion of an infected blood-meal, at a time which indicates that this induction is a response to parasite invasion of the midgut epithelium. The i...

  18. Novel Plasmodium falciparum malaria vaccines: evidence-based searching for variant surface antigens as candidates for vaccination against pregnancy-associated malaria

    DEFF Research Database (Denmark)

    Staalsoe, Trine; Jensen, Anja T R; Theander, Thor G

    2002-01-01

    to statistically significant co-variation with protection rather than on demonstration of causal relationships. We have studied the relationship between variant surface antigen-specific antibodies and clinical protection from Plasmodium falciparum malaria in general, and from pregnancy-associated malaria (PAM...

  19. Cortisol and uncomplicatedPlasmodium falciparum malaria in an area of unstable malaria transmission in eastern Sudan

    Institute of Scientific and Technical Information of China (English)

    Ibrahim EA; Kheir MM; Elhardello OA; Almahi WA; Ali NI; Elbashir MI; Ishag Adam

    2011-01-01

    Objective:To investigate the levels of serum cortisol in patients with uncomplicatedPlasmodium falciparum (P. falciparum) malaria in an area of unstable malaria transmission in eastern Sudan. Methods: The concentrations of cortisol were measured in sera of 25 patients with uncomplicated P. falciparum malaria (at presentation, 24 h and7 d later) and25 healthy volunteers using radioimmunoassay gamma counter.Results:There was no significant difference in mean(SD) of total cortisol levels in patients with malaria in comparison with the control group;602.2 (369.6)vs. 449.2(311.7)ng/mL,P=0.12. In patients with uncomplicatedP. falciparum malaria, the mean (SD) presenting cortisol levels were significantly higher in comparison to the levels on day7; 602.2 (369.6)vs.373.6(139.1)ng/mL,P=0.009. In the patients with uncomplicatedP. falciparum malaria (on presentation) cortisol levels were not correlated with initial temperature or the presenting parasitaemia.Conclusions: Thus, cortisol levels were not significantly different between the patients and the controls.

  20. [Erythrocyte polymorphism in Mali: epidemiology and resistance mechanisms against severe Plasmodium falciparum malaria].

    Science.gov (United States)

    Doumbo, Ogobara

    2007-01-01

    Homo sapiens and Plasmodium falciparum have co-evolved since the beginning of agriculture, 10,000 to 20,000 years ago. By domesticating plants and animals, humans linked their destiny to one of the main vectors of malaria, Anopheles gambiae sl complex. The biological interaction between these three species led to exchanges of genes and biochemical processes with significant mutual influence. Humans acquired mutations with selective protective advantages against serious and fatal forms of this hemosporidiosis. This is the case of hemoglobin S, hemoglobin C, hemoglobin E, thalassemias, ovalocytosis and G6PD deficiency, among others. Many epidemiological studies published since 1949 have shown a geographic link between malaria and certain erythrocyte polymorphisms. The link with hemoglobin C was discovered only recently, in 2000, initially in Mali in the Dogon population, then in Burkina Faso. Epidemiological and molecular and cellular biology studies done in Mali and elsewhere showed that the C and S alleles, and G6PD deficiency [A-], conferred significant protection against lethal forms of Plasmodium falciparum malaria. Molecular genetic studies, based on functional genomics, transcriptomics and proteomics, provided possible explanations. Advances in molecular biology and a better understanding of the immune mechanisms underlying this protection will hopefully lead to the development of effective second- and third-generation malaria vaccines. Epidemiological and fundamental research efforts have identified some of the mechanisms by which these erythrocyte polymorphisms protect against the most lethal hematozoan parasite, Plasmodium falciparum.

  1. A highly sensitive aptasensor towards Plasmodium lactate dehydrogenase for the diagnosis of malaria.

    Science.gov (United States)

    Lee, Seonghwan; Song, Kyung-Mi; Jeon, Weejeong; Jo, Hunho; Shim, Yoon-Bo; Ban, Changill

    2012-05-15

    Finding a highly sensitive diagnostic technique for malaria has challenged scientists for the last century. In the present study, we identified versatile single-strand DNA aptamers for Plasmodium lactate dehydrogenase (pLDH), a biomarker for malaria, via the Systematic Evolution of Ligands by EXponential enrichment (SELEX). The pLDH aptamers selectively bound to the target proteins with high sensitivity (K(d)=16.8-49.6 nM). The selected aptamers were characterized using an electrophoretic mobility shift assay, a quartz crystal microbalance, a fluorescence assay, and circular dichroism spectroscopy. We also designed a simple aptasensor using electrochemical impedance spectroscopy; both Plasmodium vivax LDH and Plasmodium falciparum LDH were selectively detected with a detection limit of 1 pM. Furthermore, the pLDH aptasensor clearly distinguished between malaria-positive blood samples of two major species (P. vivax and P. falciparum) and a negative control, indicating that it may be a useful tool for the diagnosis, monitoring, and surveillance of malaria.

  2. 伯氏疟原虫氯喹抗性逆转的实验观察%Search for reverser of chloroquine-resistance in Plasmodium berghei

    Institute of Scientific and Technical Information of China (English)

    吴嘉彤; 兰勤娴; 王琴美; 潘星清

    2010-01-01

    Objective To search for reverser of chloroquine-resistance in Plasmodium berghei (P.berghei) ANKA. Methods Seventy-two healthy Kunming mice were each infected with chloroquine sensitive (CS) or chloroquine resistance (CR) P. berghei ANKA respectively, then treated with various schedule of reversal agents C-2832 、D-6182 or ketotifen(Ket) respectively with or without co-administration of low dose (5%ED90) of chloroquine (CQ). Schedule 1: mice infected with CS were randomly distributed into 4 groups, 6 mice in each group, 30 min after infection,then treated i.g. with D-6182, C-2832, Ket or 0. 1% gum tragacanth(control) respectively for 5 consecutive days. The parasitemia of each experiment group was then determined by routine microscopic examination on blood smears from the tail blood of each mouse from D1 to D7.Schedule 2:mice infected with CR were randomly distriduted into 8 groups, 6 mice in each group, 3 d after infection, then treated i.g. with D-6182, C-2832, Ket, chloroquine or 0. 1% gum tragacanth (control) with or without co-administration of 12 mg/(kg · d) chloroquine (5% ED90) 2 h after the first administration for 5 consecutive days. The parasitemia of each experiment group was then determined microscopically by examination on blood smears from the tail blood of each mouse from D4 to D7. The reduction rates of each group were calculated and compared between the groups with or without treatment of reverser. Results 1. The parasitemia of mice infected with CS was going up daily from D1 to D4 and reached the peak on D4 in all groups administered with 80 mg/(kg · d) D-6182, 120 mg/(kg · d) C-2832 or 10 mg/(kg · d) Ket for5 d. From D5 the parasitemia kept going up in control group while it kept at the level of D4 in all treated groups. 2. Chloroquine 12 mg/(kg · d) administered i.g. 2 h after administration of C-2832 or D-6182 or Ket for 5 d(D3-D7) could reach 97.77%, 99.28% or 96.73% of reduction rate of parasitemia on D4 and 99.81%, 98.87% or 100

  3. High Plasmodium malariae Prevalence in an Endemic Area of the Colombian Amazon Region.

    Science.gov (United States)

    Camargo-Ayala, Paola Andrea; Cubides, Juan Ricardo; Niño, Carlos Hernando; Camargo, Milena; Rodríguez-Celis, Carlos Arturo; Quiñones, Teódulo; Sánchez-Suárez, Lizeth; Patarroyo, Manuel Elkin; Patarroyo, Manuel Alfonso

    2016-01-01

    Malaria is a worldwide public health problem; parasites from the genus Plasmodium are the aetiological agent for this disease. The parasites are mostly diagnosed by conventional microscopy-based techniques; however, their limitations have led to under-registering the reported prevalence of Plasmodium species. This study has thus been aimed at evaluating the infection and coinfection prevalence of 3 species of Plasmodium spp., in an area of the Colombian Amazon region. Blood samples were taken from 671 symptomatic patients by skin puncture; a nested PCR amplifying the 18S ssRNA region was used on all samples to determine the presence of P. vivax, P. malariae and P. falciparum. Statistical analysis determined infection and coinfection frequency; the association between infection and different factors was established. The results showed that P. vivax was the species having the greatest frequency in the study population (61.4%), followed by P. malariae (43.8%) and P. falciparum (11.8%). The study revealed that 35.8% of the population had coinfection, the P. vivax/P. malariae combination occurring most frequently (28.3%); factors such as age, geographical origin and clinical manifestations were found to be associated with triple-infection. The prevalence reported in this study differed from previous studies in Colombia; the results suggest that diagnosis using conventional techniques could be giving rise to underestimating some Plasmodium spp. species having high circulation rates in Colombia (particularly in the Colombian Amazon region). The present study's results revealed a high prevalence of P. malariae and mixed infections in the population being studied. The results provide relevant information which should facilitate updating the epidemiological panorama and species' distribution so as to include control, prevention and follow-up measures.

  4. High Plasmodium malariae Prevalence in an Endemic Area of the Colombian Amazon Region

    Science.gov (United States)

    Camargo-Ayala, Paola Andrea; Cubides, Juan Ricardo; Niño, Carlos Hernando; Camargo, Milena; Rodríguez-Celis, Carlos Arturo; Quiñones, Teódulo; Sánchez-Suárez, Lizeth; Patarroyo, Manuel Elkin

    2016-01-01

    Malaria is a worldwide public health problem; parasites from the genus Plasmodium are the aetiological agent for this disease. The parasites are mostly diagnosed by conventional microscopy-based techniques; however, their limitations have led to under-registering the reported prevalence of Plasmodium species. This study has thus been aimed at evaluating the infection and coinfection prevalence of 3 species of Plasmodium spp., in an area of the Colombian Amazon region. Blood samples were taken from 671 symptomatic patients by skin puncture; a nested PCR amplifying the 18S ssRNA region was used on all samples to determine the presence of P. vivax, P. malariae and P. falciparum. Statistical analysis determined infection and coinfection frequency; the association between infection and different factors was established. The results showed that P. vivax was the species having the greatest frequency in the study population (61.4%), followed by P. malariae (43.8%) and P. falciparum (11.8%). The study revealed that 35.8% of the population had coinfection, the P. vivax/P. malariae combination occurring most frequently (28.3%); factors such as age, geographical origin and clinical manifestations were found to be associated with triple-infection. The prevalence reported in this study differed from previous studies in Colombia; the results suggest that diagnosis using conventional techniques could be giving rise to underestimating some Plasmodium spp. species having high circulation rates in Colombia (particularly in the Colombian Amazon region). The present study’s results revealed a high prevalence of P. malariae and mixed infections in the population being studied. The results provide relevant information which should facilitate updating the epidemiological panorama and species’ distribution so as to include control, prevention and follow-up measures. PMID:27467587

  5. Optimizing the HRP-2 In Vitro Malaria Drug Susceptibility Assay Using a Reference Clone to Improve Comparisons of Plasmodium falciparum Field Isolates

    Science.gov (United States)

    2012-09-13

    available soon. Optimizing the HRP-2 in vitro malaria drug susceptibility assay using a reference clone to improve comparisons of Plasmodium falciparum...Optimizing the HRP-2 in vitro malaria drug susceptibility assay using a reference clone to improve comparisons of Plasmodium falciparum field isolates 5a...Date: 13 September 2012 14. ABSTRACT Apparent emerging artemisinin-resistant Plasmodium falciparum malaria in Southeast Asia requires development

  6. Drug intervention effects on thrombocytopenia due to Plasmodium berghei infection in mice%鼠疟原虫引起血小板减少药物干预效果的观察

    Institute of Scientific and Technical Information of China (English)

    区德锦; 韦海艳; 邹春燕; 崔立旺; 黄亚铭

    2013-01-01

    Objective To analyze the common antipyretics,antibiotics and corticosteroids on thrombocytopenia due to Plasmodium berghei infection in mice. Methods Healthy Kunming mice were intraperitoneally inoculated with Plasmodium berghei and treated with β -Iactams,quinolones, antipyretics and corticosteroids at dose of 10 times that of human dose for 3 days by irrigation or intramuscular injection when platelet count markedly below normal value.Then blood samples were obtained for every 12 hours and platelet count was recorded. Observation group consisted of five mice and each drug was tested in a group and with control group. Results The normal mice platelet count averaged for 256 × 109/L and the platelet count dropped to an average count of 90 ×109/L in each group 8 days after infection with Plasmodium berghei. The platelet count returned to 201 × 109/L in azithromycin-treated group only 3 days after treated with various antibiotics and muscular injection of aminophenazone and dexamethasone.and other antibiotics, antipyretic and corticosteroids showed no effect on thrombocytopenia recovery in mice infected with Plasmodium berghei. Conclusions Except azithromycin,aminophenazone,amoxicillin,levofloxacin and dexamethasone showed on effects on platelet recovery in mice infected with Plasmodium berghei.%目的 了解退烧药、抗生素及激素对感染鼠疟原虫引起的血小板减少是否具有恢复的效果.方法 健康昆明小鼠腹腔接种感染伯氏鼠疟原虫,当感染鼠血小板明显低于正常值后,分别采用临床常用的大环内酯类、β内酰胺类和喹诺酮类抗生素、退烧药及激素类药物按照人体治疗量的10倍灌服或肌注方法给药3d,每12h采血1次做血小板计数观察.每5只小鼠为一个观察试验组,每种药物采用一组小鼠试验观察取平均数据,并设正常对照组. 结果 正常鼠血小板平均计数为256 × 109/L.健康鼠感染鼠疟原虫后第8d,各组感

  7. Transplacental Transmission of Plasmodium falciparum in a Highly Malaria Endemic Area of Burkina Faso

    Directory of Open Access Journals (Sweden)

    Alphonse Ouédraogo

    2012-01-01

    Full Text Available Malaria congenital infection constitutes a major risk in malaria endemic areas. In this study, we report the prevalence of transplacental malaria in Burkina Faso. In labour and delivery units, thick and thin blood films were made from maternal, placental, and umbilical cord blood to determine malaria infection. A total of 1,309 mother/baby pairs were recruited. Eighteen cord blood samples (1.4% contained malaria parasites (Plasmodium falciparum. Out of the 369 (28.2% women with peripheral positive parasitemia, 211 (57.2% had placental malaria and 14 (3.8% had malaria parasites in their umbilical cord blood. The umbilical cord parasitemia levels were statistically associated with the presence of maternal peripheral parasitemia (OR=9.24, ≪0.001, placental parasitemia (OR=10.74, ≪0.001, high-density peripheral parasitemia (OR=9.62, ≪0.001, and high-density placental parasitemia (OR=4.91, =0.03. In Burkina Faso, the mother-to-child transmission rate of malaria appears to be low.

  8. Efficacy of chloroquine for the treatment of uncomplicated Plasmodium falciparum malaria in Honduras.

    Science.gov (United States)

    Mejia Torres, Rosa Elena; Banegas, Engels Ilich; Mendoza, Meisy; Diaz, Cesar; Bucheli, Sandra Tamara Mancero; Fontecha, Gustavo A; Alam, Md Tauqeer; Goldman, Ira; Udhayakumar, Venkatachalam; Zambrano, Jose Orlinder Nicolas

    2013-05-01

    Chloroquine (CQ) is officially used for the primary treatment of Plasmodium falciparum malaria in Honduras. In this study, the therapeutic efficacy of CQ for the treatment of uncomplicated P. falciparum malaria in the municipality of Puerto Lempira, Gracias a Dios, Honduras was evaluated using the Pan American Health Organization-World Health Organization protocol with a follow-up of 28 days. Sixty-eight patients from 6 months to 60 years of age microscopically diagnosed with uncomplicated P. falciparum malaria were included in the final analysis. All patients who were treated with CQ (25 mg/kg over 3 days) cleared parasitemia by day 3 and acquired no new P. falciparum infection within 28 days of follow-up. All the parasite samples sequenced for CQ resistance mutations (pfcrt) showed only the CQ-sensitive genotype (CVMNK). This finding shows that CQ remains highly efficacious for the treatment of uncomplicated P. falciparum malaria in Gracias a Dios, Honduras.

  9. Increased plasma levels of soluble IL-2R are associated with severe Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Jakobsen, P H; Morris-Jones, S; Theander, T G;

    1994-01-01

    Plasma samples from children with mild and severe Plasmodium falciparum malaria and from children with unrelated diseases were collected to investigate whether the clinical outcome of infection was associated with plasma factors which reflected the activity of different cells of the immune system....... Children with severe P. falciparum malaria had significantly higher plasma levels of soluble IL-2R than children with mild malaria. Plasma levels of IL-2R and levels of parasitaemia were significantly correlated. Neither parasitaemia nor plasma levels of tumour necrosis factor-alpha (TNF-alpha), IL-6......, lymphotoxin (LT), interferon-gamma (IFN-gamma), IL-4, soluble IL-4R or soluble CD8 differed significantly between the two groups of children with malaria. High plasma levels of soluble CD8 were associated with failure of lymphocytes to produce IFN-gamma in vitro following stimulation with P. falciparum...

  10. Defining the protein interaction network of human malaria parasite Plasmodium falciparum

    KAUST Repository

    Ramaprasad, Abhinay

    2012-02-01

    Malaria, caused by the protozoan parasite Plasmodium falciparum, affects around 225. million people yearly and a huge international effort is directed towards combating this grave threat to world health and economic development. Considerable advances have been made in malaria research triggered by the sequencing of its genome in 2002, followed by several high-throughput studies defining the malaria transcriptome and proteome. A protein-protein interaction (PPI) network seeks to trace the dynamic interactions between proteins, thereby elucidating their local and global functional relationships. Experimentally derived PPI network from high-throughput methods such as yeast two hybrid (Y2H) screens are inherently noisy, but combining these independent datasets by computational methods tends to give a greater accuracy and coverage. This review aims to discuss the computational approaches used till date to construct a malaria protein interaction network and to catalog the functional predictions and biological inferences made from analysis of the PPI network. © 2011 Elsevier Inc.

  11. 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....

  12. Plasmodium falciparum var genes expressed in children with severe malaria encode CIDRα1 domains

    DEFF Research Database (Denmark)

    Jespersen, Jakob S.; Wang, Christian W.; Mkumbaye, Sixbert I.;

    2016-01-01

    Most severe Plasmodium falciparum infections are experienced by young children. Severe symptoms are precipitated by vascular sequestration of parasites expressing a particular subset of the polymorphic P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesion molecules. Parasites binding human...... endothelial protein C receptor (EPCR) through the CIDRα1 domain of certain PfEMP1 were recently associated with severe malaria in children. However, it has remained unclear to which extend the EPCR-binding CIDRα1 domains epitomize PfEMP1 expressed in severe malaria. Here, we characterized the near full......-length transcripts dominating the var transcriptome in children with severe malaria and found that the only common feature of the encoded PfEMP1 was CIDRα1 domains. Such genes were highly and dominantly expressed in both children with severe malarial anaemia and cerebral malaria. These observations support...

  13. Multiple clinical episodes of Plasmodium falciparum malaria in a low transmission intensity setting: exposure versus immunity.

    Science.gov (United States)

    Rono, Josea; Färnert, Anna; Murungi, Linda; Ojal, John; Kamuyu, Gathoni; Guleid, Fatuma; Nyangweso, George; Wambua, Juliana; Kitsao, Barnes; Olotu, Ally; Marsh, Kevin; Osier, Faith Ha

    2015-05-13

    Epidemiological studies indicate that some children experience many more episodes of clinical malaria than their age mates in a given location. Whether this is as a result of the micro-heterogeneity of malaria transmission with some children effectively getting more exposure to infectious mosquitoes than others, or reflects a failure in the acquisition of immunity needs to be elucidated. Here, we investigated the determinants of increased susceptibility to clinical malaria by comparing the intensity of exposure to Plasmodium falciparum and the acquisition of immunity in children at the extreme ends of the over-dispersed distribution of the incidence of clinical malaria. The study was nested within a larger cohort in an area where the intensity of malaria transmission was low. We identified children who over a five-year period experienced 5 to 16 clinical malaria episodes (children at the tail-end of the over-dispersed distribution, n = 35), remained malaria-free (n = 12) or had a single episode (n = 26). We quantified antibodies against seven Plasmodium falciparum merozoite antigens in plasma obtained at six cross-sectional surveys spanning these five years. We analyzed the antibody responses to identify temporal dynamics that associate with disease susceptibility. Children experiencing multiple episodes of malaria were more likely to be parasite positive by microscopy at cross-sectional surveys (X (2) test for trend 14.72 P = 0.001) and had a significantly higher malaria exposure index, than those in the malaria-free or single episode groups (Kruskal-Wallis test P = 0.009). In contrast, the five-year temporal dynamics of anti-merozoite antibodies were similar in the three groups. Importantly in all groups, antibody levels were below the threshold concentrations previously observed to be correlated with protective immunity. We conclude that in the context of a low malaria transmission setting, susceptibility to clinical malaria is not accounted

  14. Clustered local transmission and asymptomatic Plasmodium falciparum and Plasmodium vivax malaria infections in a recently emerged, hypoendemic Peruvian Amazon community

    Directory of Open Access Journals (Sweden)

    Alvarez Eugenia

    2005-06-01

    Full Text Available Abstract Background There is a low incidence of malaria in Iquitos, Peru, suburbs detected by passive case-detection. This low incidence might be attributable to infections clustered in some households/regions and/or undetected asymptomatic infections. Methods Passive case-detection (PCD during the malaria season (February-July and an active case-detection (ACD community-wide survey (March surveyed 1,907 persons. Each month, April-July, 100-metre at-risk zones were defined by location of Plasmodium falciparum infections in the previous month. Longitudinal ACD and PCD (ACP+PCD occurred within at-risk zones, where 137 houses (573 persons were randomly selected as sentinels, each with one month of weekly active sampling. Entomological captures were conducted in the sentinel houses. Results The PCD incidence was 0.03 P. falciparum and 0.22 Plasmodium vivax infections/person/malaria-season. However, the ACD+PCD prevalence was 0.13 and 0.39, respectively. One explanation for this 4.33 and 1.77-fold increase, respectively, was infection clustering within at-risk zones and contiguous households. Clustering makes PCD, generalized to the entire population, artificially low. Another attributable-factor was that only 41% and 24% of the P. falciparum and P. vivax infections were associated with fever and 80% of the asymptomatic infections had low-density or absent parasitaemias the following week. After accounting for asymptomatic infections, a 2.6-fold increase in ACD+PCD versus PCD was attributable to clustered transmission in at-risk zones. Conclusion Even in low transmission, there are frequent highly-clustered asymptomatic infections, making PCD an inadequate measure of incidence. These findings support a strategy of concentrating ACD and insecticide campaigns in houses adjacent to houses were malaria was detected one month prior.

  15. LAMP kit for diagnosis of non-falciparum malaria in Plasmodium ovale infected patients.

    Science.gov (United States)

    Cuadros, Juan; Martin Ramírez, Alexandra; González, Iveth J; Ding, Xavier C; Perez Tanoira, Ramon; Rojo-Marcos, Gerardo; Gómez-Herruz, Peña; Rubio, Jose Miguel

    2017-01-07

    Microscopy and rapid diagnosis tests have a limited sensitivity in diagnosis of malaria by Plasmodium ovale. The LAMP kit (LoopAMP®) can be used in the field without special equipment and could have an important role in malaria control programmes in endemic areas and for malaria diagnosis in returned travellers. The performance of the Pan primer of the kit in detecting malaria by P. ovale was compared with the results of standard nPCR in samples of patients returning from P. ovale endemic areas. Plasmodium ovale positive samples (29, tested by PCR and/or microscopy) and malaria negative specimens (398, tested by microscopy and PCR) were collected in different hospitals of Europe from June 2014 to March 2016 and frozen at -20 °C. Boil and spin method was used to extract DNA from all samples and amplification was performed with LoopAMP® MALARIA kit (Eiken Chemical, Japan) in an automated turbidimeter (Eiken 500). The results of LAMP read by turbidimetry and with the naked eye were compared. The kit showed a sensitivity of 100% and a specificity of 97.24% with positive and negative predictive values of 72.5 and 100%, respectively. Naked eyed readings were in accordance with turbidimetry readings (sensitivity, 92.5%, specificity, 98.96% and positive and negative predictive values, respectively, 90.24 and 99.22%). The limit of detection of LAMP assay for P. ovale was between 0.8 and 2 parasites/µl. The Pan primer of the Malaria kit LoopAMP® can detect P. ovale at very low-levels and showed a predictive negative value of 100%. This tool can be useful in malaria control and elimination programmes and in returned travellers from P. ovale endemic areas. Naked eye readings are equivalent to automated turbidimeter readings in specimens obtained with EDTA.

  16. Epidemiology and Infectivity of Plasmodium falciparum and Plasmodium vivax Gametocytes in Relation to Malaria Control and Elimination

    Science.gov (United States)

    Bousema, Teun; Drakeley, Chris

    2011-01-01

    Summary: Malaria remains a major cause of morbidity and mortality in the tropics, with Plasmodium falciparum responsible for the majority of the disease burden and P. vivax being the geographically most widely distributed cause of malaria. Gametocytes are the sexual-stage parasites that infect Anopheles mosquitoes and mediate the onward transmission of the disease. Gametocytes are poorly studied despite this crucial role, but with a recent resurgence of interest in malaria elimination, the study of gametocytes is in vogue. This review highlights the current state of knowledge with regard to the development and longevity of P. falciparum and P. vivax gametocytes in the human host and the factors influencing their distribution within endemic populations. The evidence for immune responses, antimalarial drugs, and drug resistance influencing infectiousness to mosquitoes is reviewed. We discuss how the application of molecular techniques has led to the identification of submicroscopic gametocyte carriage and to a reassessment of the human infectious reservoir. These components are drawn together to show how control measures that aim to reduce malaria transmission, such as mass drug administration and a transmission-blocking vaccine, might better be deployed. PMID:21482730

  17. The use of activated protein C in severe Plasmodium falciparum malaria.

    Science.gov (United States)

    Rankin, L G; Austin, D L H

    2007-06-01

    A 56-year-old man presented to a peripheral hospital in New Zealand with severe Plasmodium falciparum malaria with cerebral involvement and subsequently developed multi-system organ failure. Activated protein C was used in an attempt to stop the cascade of events into multi-organ failure. Severe infection with P. falciparum is life-threatening and appears to activate a hypercoagulable state similar to that of severe sepsis. Activated protein C is currently used in the treatment of severe sepsis and may provide a new adjuvant therapy for severe P. falciparum malaria.

  18. Association of a single nucleotide polymorphism in the C-reactive protein gene (-286) with susceptibility to Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Giha, Hayder A; Nasr, Amre; Ekström, Mattias

    2010-01-01

    The role of inflammation in malaria pathogenesis is not fully understood, although C-reactive protein (CRP) may have a negative influence on host immunity to infections. An upstream polymorphism, -286 (C > T > A), in the CRP gene is known to influence CRP levels. In this study, a cohort of 192 Su...... to uncomplicated Plasmodium falciparum malaria....

  19. Morbidity from malaria and immune responses to defined Plasmodium falciparum antigens in children with sickle cell trait in The Gambia

    DEFF Research Database (Denmark)

    Allen, S J; Bennett, S; Riley, E M

    1993-01-01

    Morbidity from Plasmodium falciparum malaria and humoral and in vitro cellular immune responses to defined malaria antigens were measured in rural Gambian children with haemoglobin phenotype AS (HbAS) and in those with a normal haemoglobin (HbAA). In a survey undertaken during the dry season, HbA...

  20. Human recombinant antibodies against Plasmodium falciparum merozoite surface protein 3 cloned from peripheral blood leukocytes of individuals with immunity to malaria demonstrate antiparasitic properties

    DEFF Research Database (Denmark)

    Lundquist, Rasmus; Nielsen, Leif Kofoed; Jafarshad, Ali

    2006-01-01

    Immunoglobulins from individuals with immunity to malaria have a strong antiparasitic effect when transferred to Plasmodium falciparum malaria infected patients. One prominent target of antiparasitic antibodies is the merozoite surface antigen 3 (MSP-3). We have investigated the antibody response...

  1. 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

  2. A full-length Plasmodium falciparum recombinant circumsporozoite protein expressed by Pseudomonas fluorescens platform as a malaria vaccine candidate.

    Directory of Open Access Journals (Sweden)

    Amy R Noe

    Full Text Available The circumsporozoite protein (CSP of Plasmodium falciparum is a major surface protein, which forms a dense coat on the sporozoite's surface. Preclinical research on CSP and clinical evaluation of a CSP fragment-based RTS, S/AS01 vaccine have demonstrated a modest degree of protection against P. falciparum, mediated in part by humoral immunity and in part by cell-mediated immunity. Given the partial protective efficacy of the RTS, S/AS01 vaccine in a recent Phase 3 trial, further improvement of CSP-based vaccines is crucial. In this report, we describe the preclinical development of a full-length, recombinant CSP (rCSP-based vaccine candidate against P. falciparum malaria suitable for current Good Manufacturing Practice (cGMP production. Utilizing a novel high-throughput Pseudomonas fluorescens expression platform, we demonstrated greater efficacy of full-length rCSP as compared to N-terminally truncated versions, rapidly down-selected a promising lead vaccine candidate, and developed a high-yield purification process to express immunologically active, intact antigen for clinical trial material production. The rCSP, when formulated with various adjuvants, induced antigen-specific antibody responses as measured by enzyme-linked immunosorbent assay (ELISA and immunofluorescence assay (IFA, as well as CD4+ T-cell responses as determined by ELISpot. The adjuvanted rCSP vaccine conferred protection in mice when challenged with transgenic P. berghei sporozoites containing the P. falciparum repeat region of CSP. Furthermore, heterologous prime/boost regimens with adjuvanted rCSP and an adenovirus type 35-vectored CSP (Ad35CS showed modest improvements in eliciting CSP-specific T-cell responses and anti-malarial protection, depending on the order of vaccine delivery. Collectively, these data support the importance of further clinical development of adjuvanted rCSP, either as a stand-alone product or as one of the components in a heterologous prime

  3. Rapid diagnostic tests for diagnosing uncomplicated non-falciparum or Plasmodium vivax malaria in endemic countries

    Science.gov (United States)

    Abba, Katharine; Kirkham, Amanda J; Olliaro, Piero L; Deeks, Jonathan J; Donegan, Sarah; Garner, Paul; Takwoingi, Yemisi

    2014-01-01

    Background In settings where both Plasmodium vivax and Plasmodium falciparum infection cause malaria, rapid diagnostic tests (RDTs) need to distinguish which species is causing the patients' symptoms, as different treatments are required. Older RDTs incorporated two test lines to distinguish malaria due to P. falciparum, from malaria due to any other Plasmodium species (non-falciparum). These RDTs can be classified according to which antibodies they use: Type 2 RDTs use HRP-2 (for P. falciparum) and aldolase (all species); Type 3 RDTs use HRP-2 (for P. falciparum) and pLDH (all species); Type 4 use pLDH (fromP. falciparum) and pLDH (all species). More recently, RDTs have been developed to distinguish P. vivax parasitaemia by utilizing a pLDH antibody specific to P. vivax. Objectives To assess the diagnostic accuracy of RDTs for detecting non-falciparum or P. vivax parasitaemia in people living in malaria-endemic areas who present to ambulatory healthcare facilities with symptoms suggestive of malaria, and to identify which types and brands of commercial test best detect non-falciparum and P. vivax malaria. Search methods We undertook a comprehensive search of the following databases up to 31 December 2013: Cochrane Infectious Diseases Group Specialized Register; MEDLINE; EMBASE; MEDION; Science Citation Index; Web of Knowledge; African Index Medicus; LILACS; and IndMED. Selection criteria Studies comparing RDTs with a reference standard (microscopy or polymerase chain reaction) in blood samples from a random or consecutive series of patients attending ambulatory health facilities with symptoms suggestive of malaria in non-falciparum endemic areas. Data collection and analysis For each study, two review authors independently extracted a standard set of data using a tailored data extraction form. We grouped comparisons by type of RDT (defined by the combinations of antibodies used), and combined in meta-analysis where appropriate. Average sensitivities and

  4. Genome-wide functional analysis of plasmodium protein phosphatases reveals key regulators of parasite development and differentiation

    KAUST Repository

    Guttery, David S.

    2014-07-09

    Reversible protein phosphorylation regulated by kinases and phosphatases controls many cellular processes. Although essential functions for the malaria parasite kinome have been reported, the roles of most protein phosphatases (PPs) during Plasmodium development are unknown. We report a functional analysis of the Plasmodium berghei protein phosphatome, which exhibits high conservation with the P. falciparum phosphatome and comprises 30 predicted PPs with differential and distinct expression patterns during various stages of the life cycle. Gene disruption analysis of P. berghei PPs reveals that half of the genes are likely essential for asexual blood stage development, whereas six are required for sexual development/sporogony in mosquitoes. Phenotypic screening coupled with transcriptome sequencing unveiled morphological changes and altered gene expression in deletion mutants of two N-myristoylated PPs. These findings provide systematic functional analyses of PPs in Plasmodium, identify how phosphatases regulate parasite development and differentiation, and can inform the identification of drug targets for malaria. © 2014 The Authors.

  5. Determination of PCT on admission is a useful tool for the assessment of disease severity in travelers with imported Plasmodium falciparum malaria.

    Science.gov (United States)

    Righi, Elda; Merelli, Maria; Arzese, Alessandra; Siega, Paola Della; Scarparo, Claudio; Bassetti, Matteo

    2016-03-01

    Procalcitonin (PCT) and C-reactive protein (CRP) may be useful to predict complicated forms of malaria. A total of 30 consecutive travelers diagnosed with Plasmodium falciparum malaria over a two-year period were included in the study. Patients with complicated Plasmodium falciparum malaria showed higher levels of parasitemia (P = 0.0001), PCT (P = 0.0018), CRP (P = 0.0005), bilirubinemia (P = 0.004), and a lower platelet count (PPlasmodium falciparum malaria.

  6. Transcriptomic evidence for modulation of host inflammatory responses during febrile Plasmodium falciparum malaria

    Science.gov (United States)

    Tran, Tuan M.; Jones, Marcus B.; Ongoiba, Aissata; Bijker, Else M.; Schats, Remko; Venepally, Pratap; Skinner, Jeff; Doumbo, Safiatou; Quinten, Edwin; Visser, Leo G.; Whalen, Elizabeth; Presnell, Scott; O’Connell, Elise M.; Kayentao, Kassoum; Doumbo, Ogobara K.; Chaussabel, Damien; Lorenzi, Hernan; Nutman, Thomas B.; Ottenhoff, Tom H. M.; Haks, Mariëlle C.; Traore, Boubacar; Kirkness, Ewen F.; Sauerwein, Robert W.; Crompton, Peter D.

    2016-01-01

    Identifying molecular predictors and mechanisms of malaria disease is important for understanding how Plasmodium falciparum malaria is controlled. Transcriptomic studies in humans have so far been limited to retrospective analysis of blood samples from clinical cases. In this prospective, proof-of-principle study, we compared whole-blood RNA-seq profiles at pre-and post-infection time points from Malian adults who were either asymptomatic (n = 5) or febrile (n = 3) during their first seasonal PCR-positive P. falciparum infection with those from malaria-naïve Dutch adults after a single controlled human malaria infection (n = 5). Our data show a graded activation of pathways downstream of pro-inflammatory cytokines, with the highest activation in malaria-naïve Dutch individuals and significantly reduced activation in malaria-experienced Malians. Newly febrile and asymptomatic infections in Malians were statistically indistinguishable except for genes activated by pro-inflammatory cytokines. The combined data provide a molecular basis for the development of a pyrogenic threshold as individuals acquire immunity to clinical malaria. PMID:27506615

  7. Culex nigripalpus: a natural vector of wild turkey malaria (Plasmodium hermani) in Florida.

    Science.gov (United States)

    Forrester, D J; Nayar, J K; Foster, G W

    1980-07-01

    Durking 1977 and 1978, more than 21,000 female mosquitoes of 15 species were live-trapped in south Florida where high numbers of wild turkeys (Meleagris gallopavo) are known to harbor malarial infections. By inoculation of mosquito extracts into uninfected domestic poults, the presence of sporozoites of Plasmodium hermani was demonstrated in Culex nigrapalpus. This mosquito, previously shown to be a competent experimental vector, is believed to be the primary natural vector of wild turkey malaria in Florida.

  8. Nanovaccines for Malaria Using Plasmodium falciparum Antigen Pfs25 Attached Gold Nanoparticles

    OpenAIRE

    Kumar, Rajesh; Ray, Paresh C; Datta, Dibyadyuti; Bansal, Geetha P.; Angov, Evelina; Kumar, Nirbhay

    2015-01-01

    Malaria transmission-blocking vaccines (TBV) targeting sexual stages of the parasite represent an ideal intervention to reduce the burden of the disease and eventual elimination at the population level in endemic regions. Immune responses against sexual stage antigens impair the development of parasite inside the mosquitoes. Target antigens identified in Plasmodium falciparum include surface proteins Pfs230 and Pfs48/45 in male and female gametocytes and Pfs25 expressed in zygotes and ookinet...

  9. Common variation in the ABO glycosyltransferase is associated with susceptibility to severe Plasmodium falciparum malaria

    OpenAIRE

    Fry, Andrew E.; Griffiths, Michael J.; Auburn, Sarah; Diakite, Mahamadou; Forton, Julian T.; Green, Angela; Richardson, Anna; Wilson, Jonathan; Jallow, Muminatou; Sisay-Joof, Fatou; Pinder, Margaret; Peshu, Norbert; Williams, Thomas N.; Marsh, Kevin; Malcolm E Molyneux

    2007-01-01

    There is growing epidemiological and molecular evidence that ABO blood group affects host susceptibility to severe Plasmodium falciparum infection. The high frequency of common ABO alleles means that even modest differences in susceptibility could have a significant impact on the health of people living in malaria endemic regions. We performed an association study, the first to utilize key molecular genetic variation underlying the ABO system, genotyping >9000 individuals across 3 African pop...

  10. Nanovaccines for Malaria Using Plasmodium falciparum Antigen Pfs25 Attached Gold Nanoparticles

    OpenAIRE

    kumar, Rajesh; Ray, Paresh C.; Datta, Dibyadyuti; Bansal, Geetha P.; Angov, Evelina; Kumar, Nirbhay

    2015-01-01

    Malaria transmission-blocking vaccines (TBV) targeting sexual stages of the parasite represent an ideal intervention to reduce the burden of the disease and eventual elimination at the population level in endemic regions. Immune responses against sexual stage antigens impair the development of parasite inside the mosquitoes. Target antigens identified in Plasmodium falciparum include surface proteins Pfs230 and Pfs48/45 in male and female gametocytes and Pfs25 expressed in zygotes and ookinet...

  11. Analysis of malaria parasite phenotypes using experimental genetic crosses of Plasmodium falciparum

    OpenAIRE

    Ranford-Cartwright, Lisa C; Mwangi, Jonathan M.

    2012-01-01

    We review the principles of linkage analysis of experimental genetic crosses and their application to Plasmodium falciparum. Three experimental genetic crosses have been performed using the human malaria parasite P. falciparum. Linkage analysis of the progeny of these crosses has been used to identify parasite genes important in phenotypes such as drug resistance, parasite growth and virulence, and transmission to mosquitoes. The construction and analysis of genetic maps has been used to char...

  12. The remarkable journey of adaptation of the Plasmodium falciparum malaria parasite to New World anopheline mosquitoes.

    Science.gov (United States)

    Molina-Cruz, Alvaro; Barillas-Mury, Carolina

    2014-08-01

    Plasmodium falciparum originated in Africa, dispersed around the world as a result of human migration and had to adapt to several different indigenous anopheline mosquitoes. Anophelines from the New World are evolutionary distant form African ones and this probably resulted in a more stringent selection of Plasmodium as it adapted to these vectors. It is thought that Plasmodium has been genetically selected by some anopheline species through unknown mechanisms. The mosquito immune system can greatly limit infection and P. falciparum evolved a strategy to evade these responses, at least in part mediated by Pfs47, a highly polymorphic gene. We propose that adaptation of P. falciparum to new vectors may require evasion of their immune system. Parasites with a Pfs47 haplotype compatible with the indigenous mosquito vector would be able to survive and be transmitted. The mosquito antiplasmodial response could be an important determinant of P. falciparum population structure and could affect malaria transmission in the Americas.

  13. The remarkable journey of adaptation of the Plasmodium falciparum malaria parasite to New World anopheline mosquitoes

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    Alvaro Molina-Cruz

    2014-08-01

    Full Text Available Plasmodium falciparum originated in Africa, dispersed around the world as a result of human migration and had to adapt to several different indigenous anopheline mosquitoes. Anophelines from the New World are evolutionary distant form African ones and this probably resulted in a more stringent selection of Plasmodium as it adapted to these vectors. It is thought that Plasmodium has been genetically selected by some anopheline species through unknown mechanisms. The mosquito immune system can greatly limit infection and P. falciparum evolved a strategy to evade these responses, at least in part mediated by Pfs47, a highly polymorphic gene. We propose that adaptation of P. falciparum to new vectors may require evasion of their immune system. Parasites with a Pfs47 haplotype compatible with the indigenous mosquito vector would be able to survive and be transmitted. The mosquito antiplasmodial response could be an important determinant of P. falciparum population structure and could affect malaria transmission in the Americas.

  14. Cytokine profiling in immigrants with clinical malaria after extended periods of interrupted exposure to Plasmodium falciparum.

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    Gemma Moncunill

    Full Text Available Immunity to malaria is believed to wane with time in the absence of exposure to Plasmodium falciparum infection, but immunoepidemiological data on longevity of immunity remain controversial. We quantified serum cytokines and chemokines by suspension array technology as potential biomarkers for durability of immunity in immigrants with clinical malaria after years without parasite exposure. These were compared to serum/plasma profiles in naïve adults (travelers and semi-immune adults under continuous exposure, with malaria, along with immigrant and traveler patients without malaria. Immigrants had higher levels of IL-2, IL-5 and IL-8 compared to semi-immune adults with malaria (P≤0.0200. Time since immigration correlated with increased IL-2 (rho=0.2738P=0.0495 and IFN-γ (rho=0.3044P=0.0282. However, immigrants did not show as high IFN-γ concentrations as travelers during a first malaria episode (P<0.0001. Immigrants and travelers with malaria had higher levels of IFN-γ, IL-6, and IL-10 (P<0.0100 than patients with other diseases, and IL-8 and IL-1β were elevated in immigrants with malaria (P<0.0500. Therefore, malaria patients had a characteristic strong pro-inflammatory/Th1 signature. Upon loss of exposure, control of pro-inflammatory responses and tolerance to P. falciparum appeared to be reduced. Understanding the mechanisms to maintain non-pathogenic effector responses is important to develop new malaria control strategies.

  15. Epidemiological and clinical features of Plasmodium falciparum malaria in united nations personnel in Western Bahr el Ghazal State, South Sudan.

    Science.gov (United States)

    He, Dengming; Zhang, Yuqi; Liu, Xiaofeng; Guo, Shimin; Zhao, Donghong; Zhu, Yunjie; Li, Huaidong; Kong, Li

    2013-01-01

    Western Bahr el Ghazal State is located in northwestern South Sudan, which is a tropical area subject to Plasmodium falciparum malaria epidemics. The aim of this study is to explore the epidemiological and clinical features of Plasmodium falciparum malaria in United Nations personnel stationed in this area. From July 2006 to June 2009, epidemiological data and medical records of 678 patients with Plasmodium falciparum malaria at the U.N. level 2 hospital were analyzed. The U.N. personnel were divided into individuals not immune to Plasmodium falciparum and individuals semi-immune to Plasmodium falciparum. The patients were divided into a chemoprophylaxis group (non-immune individuals who complied with the chemoprophylaxis regimen, 582 cases) and a no/incomplete chemoprophylaxis group (non-immune individuals who either did not fully comply with chemoprophylaxis or did not use it at all and semi-immune individuals who did not use chemoprophylaxis, 96 cases). Overall morbidity was about 11.3%. There was a significant difference in the morbidity of semi-immune and non-immune individuals (1.3% vs. 15.1%, PPlasmodium falciparum malaria mainly occurred in rainy season. Gastrointestinal symptoms are an important precursor of malaria. Blood smears and rapid diagnostic tests should be performed after the onset of gastrointestinal symptoms. Appropriate chemoprophylaxis is necessary for reducing the severity of malaria.

  16. High antibody responses against Plasmodium falciparum in immigrants after extended periods of interrupted exposure to malaria.

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    Gemma Moncunill

    Full Text Available BACKGROUND: Malaria immunity is commonly believed to wane in the absence of Plasmodium falciparum exposure, based on limited epidemiological data and short-lived antibody responses in some longitudinal studies in endemic areas. METHODS: A cross-sectional study was conducted among sub-Saharan African adults residing in Spain for 1 up to 38 years (immigrants with clinical malaria (n=55 or without malaria (n=37, naïve adults (travelers with a first clinical malaria episode (n=20 and life-long malaria exposed adults from Mozambique (semi-immune adults without malaria (n=27 or with clinical malaria (n=50. Blood samples were collected and IgG levels against the erythrocytic antigens AMA-1 and MSP-1₄₂ (3D7 and FVO strains, EBA-175 and DBL-α were determined by Luminex. IgG levels against antigens on the surface of infected erythrocytes (IEs were measured by flow cytometry. RESULTS: Immigrants without malaria had lower IgG levels than healthy semi-immune adults regardless of the antigen tested (P≤0.026, but no correlation was found between IgG levels and time since migration. Upon reinfection, immigrants with malaria had higher levels of IgG against all antigens than immigrants without malaria. However, the magnitude of the response compared to semi-immune adults with malaria depended on the antigen tested. Thus, immigrants had higher IgG levels against AMA-1 and MSP-1₄₂ (P≤0.015, similar levels against EBA-175 and DBL-α, and lower levels against IEs (P≤0.016. Immigrants had higher IgG levels against all antigens tested compared to travelers (P≤0.001, both with malaria. CONCLUSIONS: Upon cessation of malaria exposure, IgG responses to malaria-specific antigens were maintained to a large extent, although the conservation and the magnitude of the recall response depended on the nature of the antigen. Studies on immigrant populations can shed light on the factors that determine the duration of malaria specific antibody responses and its

  17. Clinical factors for severity of Plasmodium falciparum malaria in hospitalized adults in Thailand.

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    Patrick Sagaki

    Full Text Available Plasmodium falciparum is a major cause of severe malaria in Southeast Asia, however, there is limited information regarding clinical factors associated with the severity of falciparum malaria from this region. We performed a retrospective case-control study to compare clinical factors and outcomes between patients with severe and non-severe malaria, and to identify clinical factors associated with the requirement for intensive care unit (ICU admission of patients with severe falciparum malaria among hospitalized adults in Southeast Asia. A total of 255 patients with falciparum malaria in the Hospital for Tropical Diseases in Bangkok, Thailand between 2006 and 2012 were included. We identified 104 patients with severe malaria (cases and 151 patients with non-severe malaria (controls. Patients with falciparum malaria with following clinical and laboratory characteristics on admission (1 referrals, (2 no prior history of malaria, (3 body temperature of >38.5°C, (4 white blood cell counts >10×10(9/µL, (5 presence of schizonts in peripheral blood smears, and (6 albumin concentrations of <3.5 g/dL, were more likely to develop severe malaria (P<0.05. Among patients with severe malaria, patients who met ≥3 of the 2010 WHO criteria had sensitivity of 79.2% and specificity of 81.8% for requiring ICU admission. Multivariate analysis identified the following as independent associated factors for severe malaria requiring ICU admission; (1 ethnicity of Thai [odds ratio (OR = 3.601, 95% confidence interval (CI = 1.011-12.822] or Myanmar [OR = 3.610, 95% CI = 1.138-11.445]; (2 referrals [OR = 3.571, 95% CI = 1.306-9.762]; (3 no prior history of malaria [OR = 5.887, 95% CI = 1.354-25.594]; and (4 albumin concentrations of <3.5 g/dL [OR = 7.200, 95% CI = 1.802-28.759]. Our findings are important for the clinical management of patients with malaria because it can help early identification of patients that could develop

  18. Clinical Factors for Severity of Plasmodium falciparum Malaria in Hospitalized Adults in Thailand

    Science.gov (United States)

    Sagaki, Patrick; Thanachartwet, Vipa; Desakorn, Varunee; Sahassananda, Duangjai; Chamnanchanunt, Supat; Chierakul, Wirongrong; Pitisuttithum, Punnee; Ruangkanchanasetr, Prajej

    2013-01-01

    Plasmodium falciparum is a major cause of severe malaria in Southeast Asia, however, there is limited information regarding clinical factors associated with the severity of falciparum malaria from this region. We performed a retrospective case-control study to compare clinical factors and outcomes between patients with severe and non-severe malaria, and to identify clinical factors associated with the requirement for intensive care unit (ICU) admission of patients with severe falciparum malaria among hospitalized adults in Southeast Asia. A total of 255 patients with falciparum malaria in the Hospital for Tropical Diseases in Bangkok, Thailand between 2006 and 2012 were included. We identified 104 patients with severe malaria (cases) and 151 patients with non-severe malaria (controls). Patients with falciparum malaria with following clinical and laboratory characteristics on admission (1) referrals, (2) no prior history of malaria, (3) body temperature of >38.5°C, (4) white blood cell counts >10×109/µL, (5) presence of schizonts in peripheral blood smears, and (6) albumin concentrations of <3.5 g/dL, were more likely to develop severe malaria (P<0.05). Among patients with severe malaria, patients who met ≥3 of the 2010 WHO criteria had sensitivity of 79.2% and specificity of 81.8% for requiring ICU admission. Multivariate analysis identified the following as independent associated factors for severe malaria requiring ICU admission; (1) ethnicity of Thai [odds ratio (OR) = 3.601, 95% confidence interval (CI) = 1.011–12.822] or Myanmar [OR = 3.610, 95% CI = 1.138–11.445]; (2) referrals [OR = 3.571, 95% CI = 1.306–9.762]; (3) no prior history of malaria [OR = 5.887, 95% CI = 1.354–25.594]; and (4) albumin concentrations of <3.5 g/dL [OR = 7.200, 95% CI = 1.802–28.759]. Our findings are important for the clinical management of patients with malaria because it can help early identification of patients that could

  19. HUBUNGAN KEPADATAN PARASIT DENGAN MANIFESTASI KLINIS PADA MALARIA Plasmodium FALCIPARUM DAN Plasmodium VIVAX

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    Rossa Avrina

    2012-07-01

    Full Text Available Malaria is still a public health problem in Indonesia. The clinical manifestation of malaria is varied, and many factors may influence its clinical manifestation. Despite the species of malaria, density of parasitemia is known related to the severity or malignancy of malaria. It is worth to analyse the clinical and laboratory data of malaria cases in monitoring dihydroartemisinin-piperaquine (DHP treatment. The extended analysed was done to assess the relationship between density of parasitemia and clinical manifestations. A subset data of monitoring DHP treatment in subjects with uncomplicated falciparum and vivax malaria in Kalimantan and Sulawesi which were consist of clinical and laboratory day-0 data was used in analysing. Clinical data were recorded through anamnesis and physical examination. Parasite density was counted by health centre microscopist and then cross-checked by certified microscopists of the Natiional Institute of Health Reseach and Development. Haemoglobin level was also measured  by health centre analyst using the existing Sahli hemoglobinmeter. For parasite density category, median is used for cut off point. In P.falciparum malaria, the cut off point is 5588/µl  and in P.vivax malaria is 3375/µl.  The relationship between parasite density and clinical manifestation in falciparum and vivax malaria was determined by bivariate and multivariate analysis with logistic regression using SPSS 17 software. The most of subject with P.falciparum and P.vivax malaria are children (<15 yeras old, male, and non indigenous. From analysis bivariate, variabels that can be analyzed by multivariate in P.falciparum malaria (p<0,25 are children under 15 years old (p=0,0 12 and Sulawesi island where subject live(p=0,163 and In P.vivax malaria is children under 15 years old (p=0,218. Because of other variables are considered biologicaly related to parasite density, therefore all variabel are analyzed with multivariate. From multivariate

  20. Induction of strain-transcending immunity against Plasmodium chabaudi adami malaria with a multiepitope DNA vaccine.

    Science.gov (United States)

    Scorza, T; Grubb, K; Smooker, P; Rainczuk, A; Proll, D; Spithill, T W

    2005-05-01

    A major goal of current malaria vaccine programs is to develop multivalent vaccines that will protect humans against the many heterologous malaria strains that circulate in endemic areas. We describe a multiepitope DNA vaccine, derived from a genomic Plasmodium chabaudi adami DS DNA expression library of 30,000 plasmids, which induces strain-transcending immunity in mice against challenge with P. c. adami DK. Segregation of this library and DNA sequence analysis identified vaccine subpools encoding open reading frames (ORFs)/peptides of >9 amino acids [aa] (the V9+ pool, 303 plasmids) and >50 aa (V50+ pool, 56 plasmids), respectively. The V9+ and V50+ plasmid vaccine subpools significantly cross-protected mice against heterologous P. c. adami DK challenge, and protection correlated with the induction of both specific gamma interferon production by splenic cells and opsonizing antibodies. Bioinformatic analysis showed that 22 of the V50+ ORFs were polypeptides conserved among three or more Plasmodium spp., 13 of which are predicted hypothetical proteins. Twenty-nine of these ORFs are orthologues of predicted Plasmodium falciparum sequences known to be expressed in the blood stage, suggesting that this vaccine pool encodes multiple blood-stage antigens. The results have implications for malaria vaccine design by providing proof-of-principle that significant strain-transcending immunity can be induced using multiepitope blood-stage DNA vaccines and suggest that both cellular responses and opsonizing antibodies are necessary for optimal protection against P. c. adami.

  1. The prognostic value of schizontaemia in imported Plasmodium falciparum malaria

    NARCIS (Netherlands)

    M.E. van Wolfswinkel (Marlies); M. De Mendonça Melo (Mariana); K. Vliegenthart-Jongbloed (Klaske); R. Koelewijn (Rob); J.J. van Hellemond (Jaap); P.J.J. van Genderen (Perry)

    2012-01-01

    textabstractBackground: In Plasmodium falciparum infection, peripheral parasite counts do not always correlate well with the sequestered parasite burden. As erythrocytes parasitized with mature trophozoites and schizonts have a high tendency to adhere to the microvascular endothelium, they are often

  2. The prognostic value of schizontaemia in imported Plasmodium falciparum malaria

    NARCIS (Netherlands)

    M.E. van Wolfswinkel (Marlies); M. De Mendonça Melo (Mariana); K. Vliegenthart-Jongbloed (Klaske); R. Koelewijn (Rob); J.J. van Hellemond (Jaap); P.J.J. van Genderen (Perry)

    2012-01-01

    textabstractBackground: In Plasmodium falciparum infection, peripheral parasite counts do not always correlate well with the sequestered parasite burden. As erythrocytes parasitized with mature trophozoites and schizonts have a high tendency to adhere to the microvascular endothelium, they are often

  3. Association of ABO blood group and Plasmodium falciparum malaria in Dore Bafeno Area, Southern Ethiopia.

    Science.gov (United States)

    Zerihun, Tewodros; Degarege, Abraham; Erko, Berhanu

    2011-08-01

    To assess the distribution of ABO blood group and their relationship with Plasmodium falciparum (P. falciparum) malaria among febrile outpatients who sought medical attention at Dore Bafeno Health Center, Southern Ethiopia. A total of 269 febrile outpatients who visited Dore Bafeno Health Center, Southern Ethiopia, were examined for malaria and also tested for ABO blood groups in January 2010. The blood specimens were collected by finger pricking, stained with Geimsa, and examined microscopically. Positive cases of the parasitemia were counted. CareStart™ Malaria Pf/Pv Combo was also used to test the blood specimens for malaria. ABO blood groups were determined by agglutination test using ERYCLONE(®) antisera. Data on socio-demographic characteristics and treatment status of the participants were also collected. Chi-square and ANOVA tests were used to assess the difference between frequencies and means, respectively. Out of a total of 269 participants, 178 (66.2%) febrile patients were found to be infected with Plasmodium parasites, among which 146 (54.3%), 28 (10.4%), and 4 (1.5%) belonged to P. falciparum, P. vivax, and mixed infections, respectively. All febrile patients were also tested for ABO blood groups and 51.3%, 23.5%, 21.9% and 3.3% were found to be blood types of O, A, B and AB, respectively. Both total malaria infection and P. falciparum infection showed significant association with blood types (Pfalciparum malaria parasitaemia for blood groups A, B, AB, and O were 3 744/µL, 1 805/µL, 5 331/µL, and 1 515/µL, respectively (Pfalciparum malaria.

  4. Plasmodium knowlesi transmission: integrating quantitative approaches from epidemiology and ecology to understand malaria as a zoonosis.

    Science.gov (United States)

    Brock, P M; Fornace, K M; Parmiter, M; Cox, J; Drakeley, C J; Ferguson, H M; Kao, R R

    2016-04-01

    The public health threat posed by zoonotic Plasmodium knowlesi appears to be growing: it is increasingly reported across South East Asia, and is the leading cause of malaria in Malaysian Borneo. Plasmodium knowlesi threatens progress towards malaria elimination as aspects of its transmission, such as spillover from wildlife reservoirs and reliance on outdoor-biting vectors, may limit the effectiveness of conventional methods of malaria control. The development of new quantitative approaches that address the ecological complexity of P. knowlesi, particularly through a focus on its primary reservoir hosts, will be required to control it. Here, we review what is known about P. knowlesi transmission, identify key knowledge gaps in the context of current approaches to transmission modelling, and discuss the integration of these approaches with clinical parasitology and geostatistical analysis. We highlight the need to incorporate the influences of fine-scale spatial variation, rapid changes to the landscape, and reservoir population and transmission dynamics. The proposed integrated approach would address the unique challenges posed by malaria as a zoonosis, aid the identification of transmission hotspots, provide insight into the mechanistic links between incidence and land use change and support the design of appropriate interventions.

  5. Antioxidant vitamin levels among preschool children with uncomplicated Plasmodium falciparum malaria in Sokoto, Nigeria

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    Aghedo FI

    2013-07-01

    Full Text Available Festus I Aghedo,1 Resqua A Shehu,2 Rabiu A Umar,2 Mohammed N Jiya,3 Osaro Erhabor4 1Department of Haematology, Usmanu Danfodiyo University Teaching Hospital, Sokoto, Nigeria; 2Department of Biochemistry, Usmanu Danfodiyo University, Sokoto, Nigeria; 3Department of Paediatrics, College of Health Sciences, Usmanu Danfodiyo University, Sokoto, Nigeria; 4Department of Haematology, Faculty of Medical Laboratory Science, Usmanu Danfodiyo University, Sokoto, Nigeria Objective: To assess antioxidant vitamin levels among preschool children with plasmodium malarial infection. Methods: We assessed antioxidant vitamin levels by using a standard procedure in 130 malaria-parasitized preschool children. Packed cell volume and parasite density were also evaluated. Forty healthy age- and gender-matched nonparasitized children were included as controls. Results: Plasmodium falciparum was the causative species in all subjects. The mean malaria parasitemia was 4529.45 ± 1237.5/µL. The mean antioxidant concentrations for vitamins A, C, and E among plasmodium-parasitized subjects were 33.15 ± 1.79 µg/dL, 0.51 ± 0.02 mg/dL, and 0.61 ± 0.02 mg/dL, respectively. The mean concentrations of vitamins A, C, and E among the non-malaria-parasitized controls were 69.72 ± 1.71 µg/dL, 1.25 ± 0.04 mg/dL, and 1.31 ± 0.04 mg/dL respectively. We observed that the mean antioxidant concentrations of vitamins A, C, and E were significantly lower among plasmodium-parasitized subjects compared with non-parasitized controls (P = 0.01. Malaria parasitemia correlated negatively with antioxidant concentrations and packed cell volume (r = -0.736 and -0.723, P = 0.001. We observed that the higher the level of parasitemia, the lower the antioxidant concentration. Conclusion: Our study has shown that the antioxidant levels in plasmodium-parasitized children in the North-West of Nigeria are low and that the more severe the malarial infection, the lower the antioxidant level and the

  6. Influences of intermittent preventive treatment and persistent multiclonal Plasmodium falciparum infections on clinical malaria risk.

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    Anne Liljander

    Full Text Available BACKGROUND: Intermittent preventive treatment (IPT of malaria involves administration of curative doses of antimalarials at specified time points to vulnerable populations in endemic areas, regardless whether a subject is known to be infected. The effect of this new intervention on the development and maintenance of protective immunity needs further understanding. We have investigated how seasonal IPT affects the genetic diversity of Plasmodium falciparum infections and the risk of subsequent clinical malaria. MATERIAL AND METHODS: The study included 2227 Ghanaian children (3-59 months who were given sulphadoxine-pyrimethamine (SP bimonthly, artesunate plus amodiaquine (AS+AQ monthly or bimonthly, or placebo monthly for six months spanning the malaria transmission season. Blood samples collected at three post-interventional surveys were analysed by genotyping of the polymorphic merozoite surface protein 2 gene. Malaria morbidity and anaemia was monitored during 12 months follow-up. RESULTS: Monthly IPT with AS+AQ resulted in a marked reduction in number of concurrent clones and only children parasite negative just after the intervention period developed clinical malaria during follow-up. In the placebo group, children without parasites as well as those infected with ≥2 clones had a reduced risk of subsequent malaria. The bimonthly SP or AS+AQ groups had similar number of clones as placebo after intervention; however, diversity and parasite negativity did not predict the risk of malaria. An interaction effect showed that multiclonal infections were only associated with protection in children without intermittent treatment. CONCLUSION: Molecular typing revealed effects of the intervention not detected by ordinary microscopy. Effective seasonal IPT temporarily reduced the prevalence and genetic diversity of P. falciparum infections. The reduced risk of malaria in children with multiclonal infections only seen in untreated children suggests that

  7. Plasmodium vivax and Plasmodium falciparum at the crossroads of exchange among islands in Vanuatu: implications for malaria elimination strategies.

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    Chim W Chan

    Full Text Available Understanding the transmission and movement of Plasmodium parasites is crucial for malaria elimination and prevention of resurgence. Located at the limit of malaria transmission in the Pacific, Vanuatu is an ideal candidate for elimination programs due to low endemicity and the isolated nature of its island setting. We analyzed the variation in the merozoite surface protein 1 (msp1 and the circumsporozoite protein (csp of P. falciparum and P. vivax populations to examine the patterns of gene flow and population structures among seven sites on five islands in Vanuatu. Genetic diversity was in general higher in P. vivax than P. falciparum from the same site. In P. vivax, high genetic diversity was likely maintained by greater extent of gene flow among sites and among islands. Consistent with the different patterns of gene flow, the proportion of genetic variance found among islands was substantially higher in P. falciparum (28.81-31.23% than in P. vivax (-0.53-3.99%. Our data suggest that the current island-by-island malaria elimination strategy in Vanuatu, while adequate for P. falciparum elimination, might need to be complemented with more centrally integrated measures to control P. vivax movement across islands.

  8. Plasmodium vivax and Plasmodium falciparum at the crossroads of exchange among islands in Vanuatu: implications for malaria elimination strategies.

    Science.gov (United States)

    Chan, Chim W; Sakihama, Naoko; Tachibana, Shin-Ichiro; Idris, Zulkarnain Md; Lum, J Koji; Tanabe, Kazuyuki; Kaneko, Akira

    2015-01-01

    Understanding the transmission and movement of Plasmodium parasites is crucial for malaria elimination and prevention of resurgence. Located at the limit of malaria transmission in the Pacific, Vanuatu is an ideal candidate for elimination programs due to low endemicity and the isolated nature of its island setting. We analyzed the variation in the merozoite surface protein 1 (msp1) and the circumsporozoite protein (csp) of P. falciparum and P. vivax populations to examine the patterns of gene flow and population structures among seven sites on five islands in Vanuatu. Genetic diversity was in general higher in P. vivax than P. falciparum from the same site. In P. vivax, high genetic diversity was likely maintained by greater extent of gene flow among sites and among islands. Consistent with the different patterns of gene flow, the proportion of genetic variance found among islands was substantially higher in P. falciparum (28.81-31.23%) than in P. vivax (-0.53-3.99%). Our data suggest that the current island-by-island malaria elimination strategy in Vanuatu, while adequate for P. falciparum elimination, might need to be complemented with more centrally integrated measures to control P. vivax movement across islands.

  9. Assessment of Therapeutic Response of Plasmodium vivax and Plasmodium falciparum to Chloroquine in a Malaria Transmission Free Area in Colombia

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    Castillo Carmen Manuela

    2002-01-01

    Full Text Available In order to determine the frequency of therapeutic failures to chloroquine (CQ in patients with malaria due to either Plasmodium falciparum or P. vivax, and to explore the usefulness of a malaria-free city as a sentinel site to monitor the emergence of drug resistance, 53 patients (44 infected with P. vivax and 9 with P. falciparum were evaluated at the Laboratory of Parasitology, Universidad del Valle in Cali, Colombia. Patients received 25 mg/kg of CQ divided in three doses over 48 h; they were followed during 28 days according to WHO/PAHO protocols. While therapeutic failures to CQ in the P. vivax group were not detected, the proportion of therapeutic failures in the P. falciparum group was high (78% and consistent with the reports from endemic areas in Colombia. The diverse origin of cases presenting therapeutic failure confirmed that P. falciparum resistant to CQ is widespread in Colombia, and further supports the change in the national antimalarial drug scheme. Monitoring of drug resistance in malaria free areas would be useful to identify sites requiring efficacy evaluation, and in some situations could be the most appropriate alternative to collect information from endemic areas where therapeutic efficacy studies are not feasible.

  10. Evidence of non-Plasmodium falciparum malaria infection in Kédougou, Sénégal.

    Science.gov (United States)

    Daniels, Rachel F; Deme, Awa Bineta; Gomis, Jules F; Dieye, Baba; Durfee, Katelyn; Thwing, Julie I; Fall, Fatou B; Ba, Mady; Ndiop, Medoune; Badiane, Aida S; Ndiaye, Yaye Die; Wirth, Dyann F; Volkman, Sarah K; Ndiaye, Daouda

    2017-01-03

    Expanded malaria control efforts in Sénégal have resulted in increased use of rapid diagnostic tests (RDT) to identify the primary disease-causing Plasmodium species, Plasmodium falciparum. However, the type of RDT utilized in Sénégal does not detect other malaria-causing species such as Plasmodium ovale spp., Plasmodium malariae, or Plasmodium vivax. Consequently, there is a lack of information about the frequency and types of malaria infections occurring in Sénégal. This study set out to better determine whether species other than P. falciparum were evident among patients evaluated for possible malaria infection in Kédougou, Sénégal. Real-time polymerase chain reaction speciation assays for P. vivax, P. ovale spp., and P. malariae were developed and validated by sequencing and DNA extracted from 475 Plasmodium falciparum-specific HRP2-based RDT collected between 2013 and 2014 from a facility-based sample of symptomatic patients from two health clinics in Kédougou, a hyper-endemic region in southeastern Sénégal, were analysed. Plasmodium malariae (n = 3) and P. ovale wallikeri (n = 2) were observed as co-infections with P. falciparum among patients with positive RDT results (n = 187), including one patient positive for all three species. Among 288 negative RDT samples, samples positive for P. falciparum (n = 24), P. ovale curtisi (n = 3), P. ovale wallikeri (n = 1), and P. malariae (n = 3) were identified, corresponding to a non-falciparum positivity rate of 2.5%. These findings emphasize the limitations of the RDT used for malaria diagnosis and demonstrate that non-P. falciparum malaria infections occur in Sénégal. Current RDT used for routine clinical diagnosis do not necessarily provide an accurate reflection of malaria transmission in Kédougou, Sénégal, and more sensitive and specific methods are required for diagnosis and patient care, as well as surveillance and elimination activities. These findings have implications for other

  11. Detection of avian malaria (Plasmodium spp.) in native land birds of American Samoa

    Science.gov (United States)

    Jarvi, S.I.; Farias, M.E.M.; Baker, H.; Freifeld, H.B.; Baker, P.E.; Van Gelder, E.; Massey, J.G.; Atkinson, C.T.

    2003-01-01

    This study documents the presence of Plasmodium spp. in landbirds of central Polynesia. Blood samples collected from eight native and introduced species from the island of Tutuila, American Samoa were evaluated for the presence of Plasmodium spp. by nested rDNA PCR, serology and/or microscopy. A total of 111/188 birds (59%) screened by nested PCR were positive. Detection of Plasmodium spp. was verified by nucleotide sequence comparisons of partial 18S ribosomal RNA and TRAP (thrombospondin-related anonymous protein) genes using phylogenetic analyses. All samples screened by immunoblot to detect antibodies that cross-react with Hawaiian isolates of Plasmodium relictum (153) were negative. Lack of cross-reactivity is probably due to antigenic differences between the Hawaiian and Samoan Plasmodium isolates. Similarly, all samples examined by microscopy (214) were negative. The fact that malaria is present, but not detectable by blood smear evaluation is consistent with low peripheral parasitemia characteristic of chronic infections. High prevalence of apparently chronic infections, the relative stability of the native land bird communities, and the presence of mosquito vectors which are considered endemic and capable of transmitting avian Plasmodia, suggest that these parasites are indigenous to Samoa and have a long coevolutionary history with their hosts.

  12. Molecular Epidemiology of Plasmodium falciparum Malaria Outbreak, Tumbes, Peru, 2010-2012.

    Science.gov (United States)

    Baldeviano, G Christian; Okoth, Sheila Akinyi; Arrospide, Nancy; Gonzalez, Rommell V; Sánchez, Juan F; Macedo, Silvia; Conde, Silvia; Tapia, L Lorena; Salas, Carola; Gamboa, Dionicia; Herrera, Yeni; Edgel, Kimberly A; Udhayakumar, Venkatachalam; Lescano, Andrés G

    2015-05-01

    During 2010-2012, an outbreak of 210 cases of malaria occurred in Tumbes, in the northern coast of Peru, where no Plasmodium falciparum malaria case had been reported since 2006. To identify the source of the parasite causing this outbreak, we conducted a molecular epidemiology investigation. Microsatellite typing showed an identical genotype in all 54 available isolates. This genotype was also identical to that of parasites isolated in 2010 in the Loreto region of the Peruvian Amazon and closely related to clonet B, a parasite lineage previously reported in the Amazon during 1998-2000. These findings are consistent with travel history of index case-patients. DNA sequencing revealed mutations in the Pfdhfr, Pfdhps, Pfcrt, and Pfmdr1 loci, which are strongly associated with resistance to chloroquine and sulfadoxine/pyrimethamine, and deletion of the Pfhrp2 gene. These results highlight the need for timely molecular epidemiology investigations to trace the parasite source during malaria reintroduction events.

  13. Malaria-induced acquisition of antibodies to Plasmodium falciparum variant surface antigens

    DEFF Research Database (Denmark)

    Ofori, Michael F; Dodoo, Daniel; Staalsoe, Trine

    2002-01-01

    antibody responses to other parasite isolates are relatively unaffected. However, the detailed kinetics of this VSA antibody acquisition are unknown and hence were the aim of this study. We show that P. falciparum malaria in Ghanaian children generally caused a rapid and sustained increase in variant...... donors (the malaria patient). The data from this first detailed longitudinal study of acquisition of VSA antibodies support the hypothesis that naturally acquired protective immunity to P. falciparum malaria is mediated, at least in part, by VSA-specific antibodies.......In areas of intense Plasmodium falciparum transmission, protective immunity is acquired during childhood in parallel with acquisition of agglutinating antibodies to parasite-encoded variant surface antigens (VSA) expressed on parasitized red blood cells. In a semi-immune child in such an area...

  14. Molecular Epidemiology of Plasmodium falciparum Malaria Outbreak, Tumbes, Peru, 2010–2012

    Science.gov (United States)

    Okoth, Sheila Akinyi; Arrospide, Nancy; Gonzalez, Rommell V.; Sánchez, Juan F.; Macedo, Silvia; Conde, Silvia; Tapia, L. Lorena; Salas, Carola; Gamboa, Dionicia; Herrera, Yeni; Edgel, Kimberly A.; Udhayakumar, Venkatachalam; Lescano, Andrés G.

    2015-01-01

    During 2010–2012, an outbreak of 210 cases of malaria occurred in Tumbes, in the northern coast of Peru, where no Plasmodium falciparum malaria case had been reported since 2006. To identify the source of the parasite causing this outbreak, we conducted a molecular epidemiology investigation. Microsatellite typing showed an identical genotype in all 54 available isolates. This genotype was also identical to that of parasites isolated in 2010 in the Loreto region of the Peruvian Amazon and closely related to clonet B, a parasite lineage previously reported in the Amazon during 1998–2000. These findings are consistent with travel history of index case-patients. DNA sequencing revealed mutations in the Pfdhfr, Pfdhps, Pfcrt, and Pfmdr1 loci, which are strongly associated with resistance to chloroquine and sulfadoxine/pyrimethamine, and deletion of the Pfhrp2 gene. These results highlight the need for timely molecular epidemiology investigations to trace the parasite source during malaria reintroduction events. PMID:25897626

  15. Plasmodium falciparum malaria importation from Africa to China and its mortality: an analysis of driving factors

    Science.gov (United States)

    Lai, Shengjie; Wardrop, Nicola A.; Huang, Zhuojie; Bosco, Claudio; Sun, Junling; Bird, Tomas; Wesolowski, Amy; Zhou, Sheng; Zhang, Qian; Zheng, Canjun; Li, Zhongjie; Tatem, Andrew J.; Yu, Hongjie

    2016-12-01

    Plasmodium falciparum malaria importation from Africa to China is rising with increasing Chinese overseas investment and international travel. Identifying networks and drivers of this phenomenon as well as the contributors to high case-fatality rate is a growing public health concern to enable efficient response. From 2011-2015, 8653 P. falciparum cases leading to 98 deaths (11.3 per 1000 cases) were imported from 41 sub-Saharan countries into China, with most cases (91.3%) occurring in labour-related Chinese travellers. Four strongly connected groupings of origin African countries with destination Chinese provinces were identified, and the number of imported cases was significantly associated with the volume of air passengers to China (P = 0.006), parasite prevalence in Africa (P falciparum malaria importation to China can serve to refine malaria elimination strategies and the management of cases, and high risk groups and regions should be targeted.

  16. 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.

  17. Falling Plasmodium knowlesi Malaria Death Rate among Adults despite Rising Incidence, Sabah, Malaysia, 2010-2014.

    Science.gov (United States)

    Rajahram, Giri S; Barber, Bridget E; William, Timothy; Grigg, Matthew J; Menon, Jayaram; Yeo, Tsin W; Anstey, Nicholas M

    2016-01-01

    Deaths from Plasmodium knowlesi malaria have been linked to delayed parenteral treatment. In Malaysia, early intravenous artesunate is now recommended for all severe malaria cases. We describe P. knowlesi fatalities in Sabah, Malaysia, during 2012-2014 and report species-specific fatality rates based on 2010-2014 case notifications. Sixteen malaria-associated deaths (caused by PCR-confirmed P. knowlesi [7], P. falciparum [7], and P. vivax [1] and microscopy-diagnosed "P. malariae" [1]) were reported during 2012-2014. Six patients with severe P. knowlesi malaria received intravenous artesunate at hospital admission. For persons ≥15 years of age, overall fatality rates during 2010-2014 were 3.4, 4.2, and 1.0 deaths/1,000 P. knowlesi, P. falciparum, and P. vivax notifications, respectively; P. knowlesi-associated fatality rates fell from 9.2 to 1.6 deaths/1,000 notifications. No P. knowlesi-associated deaths occurred among children, despite 373 notified cases. Although P. knowlesi malaria incidence is rising, the notification-fatality rate has decreased, likely due to improved use of intravenous artesunate.

  18. Correlation of interleukin-4 levels with Plasmodium falciparum malaria parasitaemia in Sudanese children.

    Science.gov (United States)

    Elhussein, A B; Huneif, M A; Naeem, A; Fadlelseed, O E; Babiker, W G; Rahma, N E A A; Ahmed, S A M; Ayed, I A M; Shalayel, M H F

    2015-12-01

    This study aimed to measure the level of interleukin-4 (IL-4) in the serum of children patients with falciparum malaria and to correlate the production of this cytokine with the severity of malaria parasitaemia. One hundred ten patients with malaria participated in this study (53 males and 57 females) and their results were compared with that of 60 healthy control subjects. Their ages ranged between 6 months and 15 years. For the detection of parasitaemia, a calibrated thick-smear technique was used with standard Giemsa staining. For designation of the relative parasite count, a simple code from one to four crosses is used according to the criteria mentioned by Gilles and Warrell. The blood samples were assessed for IL-4 using enzyme-linked immunosorbent assay (ELISA) technique. Thirty-three malaria patients (30.27%) had one cross (+) parasitaemia, 13 patients (11.93%) had (++) parasitaemia, 24 patients (22.02%) had (+++) parasitaemia and 39 patients (35.78%) had (++++) parasitaemia. There was a significant difference (P0.0001). It was concluded that elevation of serum IL-4 in Sudanese children suffering from Plasmodium falciparum malaria is correlated with the severity of malaria hyperparasitaemia rather than with the severity of the disease.

  19. Liver changes in severe Plasmodium falciparum malaria: histopathology, apoptosis and nuclear factor kappa B expression

    Science.gov (United States)

    2014-01-01

    Background Liver involvement in severe Plasmodium falciparum infection is commonly a significant cause of morbidity and mortality among humans. The clinical presentation of jaundice often reflects a certain degree of liver damage. This study investigated the liver pathology of severe P. falciparum malaria as well as the regulation and occurrence of apoptosis in cellular components of formalin-fixed, paraffin-embedded liver tissues. Methods The liver tissues used in the study came from patients who died from P. falciparum malaria with hyperbilirubinaemia (total bilirubin (TB) ≥ 51.3 μmol/L or 3 mg/dl) (12 cases), P. falciparum malaria without hyperbilirubinaemia (TB falciparum malaria were associated with higher TB level. Significant correlations were found between NF-κB p65 expression and apoptosis in Kupffer cells and lymphocytes in the portal tracts. Conclusions Hyperplastic Kupffer cells and portal tract inflammation are two main features found in the liver tissues of severe P. falciparum malaria cases. In addition, NF-κB is associated with Kupffer cells and lymphocyte apoptosis in severe P. falciparum malaria. PMID:24636003

  20. The return of chloroquine-susceptible Plasmodium falciparum malaria in Zambia.

    Science.gov (United States)

    Mwanza, Sydney; Joshi, Sudhaunshu; Nambozi, Michael; Chileshe, Justin; Malunga, Phidelis; Kabuya, Jean-Bertin Bukasa; Hachizovu, Sebastian; Manyando, Christine; Mulenga, Modest; Laufer, Miriam

    2016-12-05

    Plasmodium falciparum resistance to anti-malarial drugs remains a major obstacle to malaria control and elimination. The parasite has developed resistance to every anti-malarial drug introduced for wide-scale treatment. However, the spread of resistance may be reversible. Malawi was the first country to discontinue chloroquine use due to widespread resistance. Within a decade of the removal of drug pressure, the molecular marker of chloroquine-resistant malaria had disappeared and the drug was shown to have excellent clinical efficacy. Many countries have observed decreases in the prevalence of chloroquine resistance with the discontinuation of chloroquine use. In Zambia, chloroquine was used as first-line treatment for uncomplicated malaria until treatment failures led the Ministry of Health to replace it with artemether-lumefantrine in 2003. Specimens from a recent study were analysed to evaluate prevalence of chloroquine-resistant malaria in Nchelenge district a decade after chloroquine use was discontinued. Parasite DNA was extracted from dried blood spots collected by finger-prick in pregnant women who were enrolling in a clinical trial. The specimens underwent pyrosequencing to determine the genotype of the P. falciparum chloroquine resistance transporter, the gene that is associated with CQ resistance. Three-hundred and two specimens were successfully analysed. No chloroquine-resistant genotypes were detected. The study found the disappearance of chloroquine-resistant malaria after the removal of chloroquine drug pressure. Chloroquine may have a role for malaria prevention or treatment in Zambia and throughout the region in the future.

  1. The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015.

    Science.gov (United States)

    Bhatt, S; Weiss, D J; Cameron, E; Bisanzio, D; Mappin, B; Dalrymple, U; Battle, K E; Moyes, C L; Henry, A; Eckhoff, P A; Wenger, E A; Briët, O; Penny, M A; Smith, T A; Bennett, A; Yukich, J; Eisele, T P; Griffin, J T; Fergus, C A; Lynch, M; Lindgren, F; Cohen, J M; Murray, C L J; Smith, D L; Hay, S I; Cibulskis, R E; Gething, P W

    2015-10-01

    Since the year 2000, a concerted campaign against malaria has led to unprecedented levels of intervention coverage across sub-Saharan Africa. Understanding the effect of this control effort is vital to inform future control planning. However, the effect of malaria interventions across the varied epidemiological settings of Africa remains poorly understood owing to the absence of reliable surveillance data and the simplistic approaches underlying current disease estimates. Here we link a large database of malaria field surveys with detailed reconstructions of changing intervention coverage to directly evaluate trends from 2000 to 2015, and quantify the attributable effect of malaria disease control efforts. We found that Plasmodium falciparum infection prevalence in endemic Africa halved and the incidence of clinical disease fell by 40% between 2000 and 2015. We estimate that interventions have averted 663 (542-753 credible interval) million clinical cases since 2000. Insecticide-treated nets, the most widespread intervention, were by far the largest contributor (68% of cases averted). Although still below target levels, current malaria interventions have substantially reduced malaria disease incidence across the continent. Increasing access to these interventions, and maintaining their effectiveness in the face of insecticide and drug resistance, should form a cornerstone of post-2015 control strategies.

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

    Directory of Open Access Journals (Sweden)

    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

  3. Evaluating experimental cerebral malaria using oxidative stress indicator OKD48 mice.

    Science.gov (United States)

    Imai, Takashi; Iwawaki, Takao; Akai, Ryoko; Suzue, Kazutomo; Hirai, Makoto; Taniguchi, Tomoyo; Okada, Hiroko; Hisaeda, Hajime

    2014-09-01

    Cerebral malaria is a fatal complication of malaria. Conventional methods for evaluating experimental cerebral malaria have several drawbacks. Therefore, we aimed to develop an easy-to-use method for evaluating experimental cerebral malaria using OKD48 (Keap1-dependent Oxidative stress Detector, No-48-luciferase) mice to evaluate oxidative stress. OKD48 mice infected with Plasmodium berghei ANKA strain (PbA) suffered from experimental cerebral malaria and oxidative stress was successfully detected in the brains of living OKD48 mice developing experimental cerebral malaria. Oxidative stress in the brain was dependent on the development of experimental cerebral malaria, as prevention of experimental cerebral malaria did not elicit oxidative stress. We provide a novel evaluation method for experimental cerebral malaria using oxidative stress indicator OKD48 mice.

  4. 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.

  5. Natural infection of Plasmodium brasilianum in humans: Man and monkey share quartan malaria parasites in the Venezuelan Amazon.

    Science.gov (United States)

    Lalremruata, Albert; Magris, Magda; Vivas-Martínez, Sarai; Koehler, Maike; Esen, Meral; Kempaiah, Prakasha; Jeyaraj, Sankarganesh; Perkins, Douglas Jay; Mordmüller, Benjamin; Metzger, Wolfram G

    2015-09-01

    The quartan malaria parasite Plasmodium malariae is the widest spread and best adapted human malaria parasite. The simian Plasmodium brasilianum causes quartan fever in New World monkeys and resembles P. malariae morphologically. Since the genetics of the two parasites are nearly identical, differing only in a range of mutations expected within a species, it has long been speculated that the two are the same. However, no naturally acquired infection with parasites termed as P. brasilianum has been found in humans until now. We investigated malaria cases from remote Yanomami indigenous communities of the Venezuelan Amazon and analyzed the genes coding for the circumsporozoite protein (CSP) and the small subunit of ribosomes (18S) by species-specific PCR and capillary based-DNA sequencing. Based on 18S rRNA gene sequencing, we identified 12 patients harboring malaria parasites which were 100% identical with P. brasilianum isolated from the monkey, Alouatta seniculus. Translated amino acid sequences of the CS protein gene showed identical immunodominant repeat units between quartan malaria parasites isolated from both humans and monkeys. This study reports, for the first time, naturally acquired infections in humans with parasites termed as P. brasilianum. We conclude that quartan malaria parasites are easily exchanged between humans and monkeys in Latin America. We hypothesize a lack of host specificity in mammalian hosts and consider quartan malaria to be a true anthropozoonosis. Since the name P. brasilianum suggests a malaria species distinct from P. malariae, we propose that P. brasilianum should have a nomenclatorial revision in case further research confirms our findings. The expansive reservoir of mammalian hosts discriminates quartan malaria from other Plasmodium spp. and requires particular research efforts.

  6. [Evaluation of imported Plasmodium falciparum malaria cases: the use of polymerase chain reaction in diagnosis].

    Science.gov (United States)

    Demiraslan, Hayati; Erdoğan, Emrah; Türe, Zeynep; Kuk, Salih; Yazar, Süleyman; Metan, Gökhan

    2013-10-01

    Malaria affecting almost half of the world population continues to be an important health problem. Although domestic malaria cases have been decreasing in Turkey recently, cases caused by Plasmodium falciparum have increased due to the frequent travelling to Africa. The aims of this study were to evaluate demographic characteristics, clinical and laboratory findings in cases with falciparum malaria who attended to our clinic in 2012-2013 period, and the impact of polymerase chain reaction (PCR) for diagnosis. Nine patients evaluated were all male with a mean age of 34.3 (age range: 18-48) years, with the history of travel to Africa. Six cases did not take prophylaxis against malaria and other three cases used insufficient time. Mean duration of symptoms after return was 18.4 (range: 1-75) days, and the patients were admitted to the clinic within a mean of 5.2 (range: 1-15) days. Two patients had leucopenia, two patients had anemia, and eight patients had thrombocytopenia on admission. Alanine aminotransferase (ALT) levels in four cases and total bilirubin levels of six cases were over upper normal limits. Definitive diagnosis of cases was performed with the detection of ring and/or gametocytes forms of the parasite in Giemsa-stained peripheral blood smears. Furthermore, samples from seven patients were studied by nested PCR by using genus (Plasmodium rPLU 1 and 5) and species (rFAL 1 and 2, rVIV 1 and 2, rMAL 1 and 2, rOVA 1 and 2) specific primers. All of these seven samples yielded positive results with primers specific for P.falciparum ssrRNA. In the treatment, arthemeter/lumefantrin and doxycycline combination was used in seven patients, while intravenous artesunate and doxycycline combination was given to two patients, resulting with complete cure. Mean duration for the resolving of fever was 3.3 days, and mean duration for clearing the parasitemia from peripheral blood was 4.9 days. Initial ALT values and the duration of fever resolution (-796; p= 0.010), as

  7. TOLLIP gene variant is associated with Plasmodium vivax malaria in the Brazilian Amazon.

    Science.gov (United States)

    Brasil, Larissa W; Barbosa, Laila R A; de Araujo, Felipe J; da Costa, Allyson G; da Silva, Luan D O; Pinheiro, Suzana K; de Almeida, Anne C G; Kuhn, Andrea; Vitor-Silva, Sheila; de Melo, Gisely C; Monteiro, Wuelton M; de Lacerda, Marcus V G; Ramasawmy, Rajendranath

    2017-03-13

    Toll-interacting protein is a negative regulator in the TLR signaling cascade, particularly by impeding the TLR2 and, TLR4 pathway. Recently, TOLLIP was shown to regulate human TLR signaling pathways. Two common TOLLIP polymorphisms (rs5743899 and rs3750920) were reported to be influencing IL-6, TNF and IL-10 expression. In this study, TOLLIP variants were investigated to their relation to Plasmodium vivax malaria in the Brazilian Amazon. This cohort study was performed in the municipalities of Careiro and, Manaus, in Western Brazilian Amazon. A total of 319 patients with P. vivax malaria and, 263 healthy controls with no previous history of malaria were included in the study. Genomic DNA was extracted from blood collected on filter paper, using the QIAamp(®) DNA Mini Kit, according to the manufacturer's suggested protocol. The rs5743899 and rs3750920 polymorphisms of the TOLLIP gene were typed by PCR-RFLP. Homozygous individuals for the rs3750920 T allele gene had twice the risk of developing malaria when compared to individuals homozygous for the C allele (OR 2.0 [95% CI 1.23-3.07]; p = 0.004). In the dominant model, carriers the C allele indicates protection to malaria, carriers of the C allele were compared to individuals with the T allele, and the difference is highly significant (OR 0.52 [95% CI 0.37-0.76]; p = 0.0006). The linkage disequilibrium between the two polymorphisms was weak (r(2) = 0.037; D' = 0.27). These findings suggest that genes involved in the TLRs-pathway may be involved in malaria susceptibility. The association of the TOLLIP rs3750920 T allele with susceptibility to malaria further provides evidence that genetic variations in immune response genes may predispose individuals to malaria.

  8. Combined measurement of soluble and cellular ICAM-1 among children with Plasmodium falciparum malaria in Uganda

    Directory of Open Access Journals (Sweden)

    Cserti-Gazdewich Christine M

    2010-08-01

    Full Text Available Abstract Background Intercellular adhesion molecule-1 (ICAM-1 is a cytoadhesion molecule implicated in the pathogenesis of Plasmodium falciparum malaria. Elevated levels of soluble ICAM-1 (sICAM-1 have previously been reported with increased malaria disease severity. However, studies have not yet examined both sICAM-1 concentrations and monocyte ICAM-1 expression in the same cohort of patients. To better understand the relationship of soluble and cellular ICAM-1 measurements in malaria, both monocyte ICAM-1 expression and sICAM-1 concentration were measured in children with P. falciparum infection exhibiting a spectrum of clinical severity. Methods Samples were analysed from 160 children, aged 0.5 to 10.8 years, with documented P. falciparum malaria in Kampala, Uganda. The patients belonged to one of three pre-study defined groups: uncomplicated malaria (UM, severe non-fatal malaria (SM-s, and fatal malaria (SM-f. Subset analysis was done on those with cerebral malaria (CM or severe malaria anaemia (SMA. Monocyte ICAM-1 was measured by flow cytometry. sICAM-1 was measured by enzyme immunoassay. Results Both sICAM-1 and monocyte cell-surface ICAM-1 followed a log-normal distribution. Median sICAM-1 concentrations increased with greater severity-of-illness: 279 ng/mL (UM, 462 ng/mL (SM-s, and 586 ng/mL (SM-f, p Conclusion In this cohort of children with P. falciparum malaria, sICAM-1 levels were associated with severity-of-illness. Patients with UM had higher monocyte ICAM-1 expression consistent with a role for monocyte ICAM-1 in immune clearance during non-severe malaria. Among the subsets of patients with either SMA or CM, monocyte ICAM-1 levels were higher in CM, consistent with the role of ICAM-1 as a marker of cytoadhesion. Categories of disease in pediatric malaria may exhibit specific combinations of soluble and cellular ICAM-1 expression.

  9. Asthma and atopic dermatitis are associated with increased risk of clinical Plasmodium falciparum malaria

    Science.gov (United States)

    Herrant, Magali; Loucoubar, Cheikh; Bassène, Hubert; Gonçalves, Bronner; Boufkhed, Sabah; Diene Sarr, Fatoumata; Fontanet, Arnaud; Tall, Adama; Baril, Laurence; Mercereau-Puijalon, Odile; Mécheri, Salaheddine; Sakuntabhai, Anavaj; Paul, Richard

    2013-01-01

    Objectives To assess the impact of atopy and allergy on the risk of clinical malaria. Design A clinical and immunological allergy cross-sectional survey in a birth cohort of 175 children from 1 month to 14 years of age followed for up to 15 years in a longitudinal open cohort study of malaria in Senegal. Malaria incidence data were available for 143 of these children (aged 4 months to 14 years of age) for up to 15 years. Mixed-model regression analysis was used to determine the impact of allergy status on malaria incidence, adjusting for age, gender, sickle-cell trait and force of infection. Main outcome measures Asthma, allergic rhinoconjunctivitis and atopic dermatitis status, the number of clinical Plasmodium falciparum malaria episodes since birth and associated parasite density. Results 12% of the children were classified as asthmatic and 10% as having atopic dermatitis. These groups had respectively a twofold (OR 2.12 95%; CI 1.46 to 3.08; p=8×10−5) and threefold (OR 3.15; 1.56 to 6.33; p=1.3×10−3) increase in the risk of clinical P falciparum malaria once older than the age of peak incidence of clinical malaria (3–4 years of age). They also presented with higher P falciparum parasite densities (asthma: mean 105.3 parasites/μL±SE 41.0 vs 51.3±9.7; p=6.2×10−3. Atopic dermatitis: 135.4±70.7 vs 52.3±11.0; p=0.014). There was no effect of allergy on the number of non-malaria clinical presentations. Individuals with allergic rhinoconjunctivitis did not have an increased risk of clinical malaria nor any difference in parasite densities. Conclusions These results demonstrate that asthma and atopic dermatitis delay the development of clinical immunity to P falciparum. Despite the encouraging decrease in malaria incidence rates in Africa, a significant concern is the extent to which the increase in allergy will exacerbate the burden of malaria. Given the demonstrated antiparasitic effect of antihistamines, administration to atopic

  10. Schistosoma co-infection protects against brain pathology but does not prevent severe disease and death in a murine model of cerebral malaria.

    Science.gov (United States)

    Bucher, Kirsten; Dietz, Klaus; Lackner, Peter; Pasche, Bastian; Fendel, Rolf; Mordmüller, Benjamin; Ben-Smith, Anne; Hoffmann, Wolfgang H

    2011-01-01

    Co-infections of helminths and malaria parasites are common in human populations in most endemic areas. It has been suggested that concomitant helminth infections inhibit the control of malaria parasitemia but down-modulate severe malarial disease. We tested this hypothesis using a murine co-infection model of schistosomiasis and cerebral malaria. C57BL/6 mice were infected with Schistosoma mansoni and 8-9 weeks later, when Schistosoma infection was patent, mice were co-infected with Plasmodium berghei ANKA strain. We found that a concomitant Schistosoma infection increased parasitemia at the beginning of the P. berghei infection. It did not protect against P. berghei-induced weight loss and hypothermia, and P. berghei-mono-infected as well as S. mansoni-P. berghei-co-infected animals showed a high case fatality between days 6 and 8 of malarial infection. However, co-infection significantly reduced P. berghei-induced brain pathology. Over 40% of the S. mansoni-P. berghei-co-infected animals that died during this period were completely protected against haemorrhaging, plugging of blood vessels and infiltration, indicating that mortality in these animals was not related to cerebral disease. Schistosoma mansoni-P. berghei-co-infected mice had elevated plasma concentrations of IL-5 and IL-13 and on day 6 lower levels of IFN-γ, IL-10, monocyte chemoattractant protein-1 (MCP-1) and monokine induced by IFN-γ (MIG) than P. berghei-mono-infected mice. We conclude that in P. berghei infections, disease and early death are caused by distinct pathogenic mechanisms, which develop in parallel and are differentially influenced by the immune response to S. mansoni. This might explain why, in co-infected mice, death could be induced in the absence of brain pathology.

  11. A scalable pipeline for highly effective genetic modification of a malaria parasite

    KAUST Repository

    Pfander, Claudia

    2011-10-23

    In malaria parasites, the systematic experimental validation of drug and vaccine targets by reverse genetics is constrained by the inefficiency of homologous recombination and by the difficulty of manipulating adenine and thymine (A+T)-rich DNA of most Plasmodium species in Escherichia coli. We overcame these roadblocks by creating a high-integrity library of Plasmodium berghei genomic DNA (>77% A+T content) in a bacteriophage N15-based vector that can be modified efficiently using the lambda Red method of recombineering. We built a pipeline for generating P. berghei genetic modification vectors at genome scale in serial liquid cultures on 96-well plates. Vectors have long homology arms, which increase recombination frequency up to tenfold over conventional designs. The feasibility of efficient genetic modification at scale will stimulate collaborative, genome-wide knockout and tagging programs for P. berghei. © 2011 Nature America, Inc. All rights reserved.

  12. A scalable pipeline for highly effective genetic modification of a malaria parasite.

    Science.gov (United States)

    Pfander, Claudia; Anar, Burcu; Schwach, Frank; Otto, Thomas D; Brochet, Mathieu; Volkmann, Katrin; Quail, Michael A; Pain, Arnab; Rosen, Barry; Skarnes, William; Rayner, Julian C; Billker, Oliver

    2011-10-23

    In malaria parasites, the systematic experimental validation of drug and vaccine targets by reverse genetics is constrained by the inefficiency of homologous recombination and by the difficulty of manipulating adenine and thymine (A+T)-rich DNA of most Plasmodium species in Escherichia coli. We overcame these roadblocks by creating a high-integrity library of Plasmodium berghei genomic DNA (>77% A+T content) in a bacteriophage N15-based vector that can be modified efficiently using the lambda Red method of recombineering. We built a pipeline for generating P. berghei genetic modification vectors at genome scale in serial liquid cultures on 96-well plates. Vectors have long homology arms, which increase recombination frequency up to tenfold over conventional designs. The feasibility of efficient genetic modification at scale will stimulate collaborative, genome-wide knockout and tagging programs for P. berghei.

  13. [Falciform anemia and Plasmodium falciparum malaria: a threat to flap survival?].

    Science.gov (United States)

    Mariéthoz, S; Pittet, B; Loutan, L; Humbert, J; Montandon, D

    1999-02-01

    Plasmodium falciparum malaria, a parasitic disease, and sickle cell anemia, a hereditary disease, are two diseases affecting erythrocyte cycle, occurring with a high prevalence in tropical Africa. They may induce microthrombosis inducing vaso-occlusion, organ dysfunction and flap necrosis. During the acute phase of Plasmodium falciparum malaria, destruction of parasitized and healthy erythrocytes, release of parasite and erythrocyte material into the circulation, and secondary host reaction occur. Plasmodium falciparum infected erythrocytes also sequester in the microcirculation of vital organs and may interfere with microcirculatory flow in the flap during the postoperative period. The lower legs of homozygous sickle cell anemia patients are areas of marginal vascularity where minor abrasions become foci of inflammation. Inflammation results in decreased local oxygen tension, sickling of erythrocytes, increased blood viscosity and thrombosis with consequent ischemia, tissue breakdown and leg ulcer. Tissue transfer has become the procedure of choice for reconstruction of the lower third of the leg although flaps may become necrotic. The aim of this study is to analyse circumstances predisposing to surgical complications and to define preventive and therapeutic measures. A review of the literature will describe the current research and the new perspectives to treat sickle cell anemia, for example hydroxyurea and vasoactive substances (pentoxifylline, naftidrofuryl, buflomedil).

  14. DNA Repair Mechanisms and Their Biological Roles in the Malaria Parasite Plasmodium falciparum

    Science.gov (United States)

    Lee, Andrew H.; Symington, Lorraine S.

    2014-01-01

    SUMMARY Research into the complex genetic underpinnings of the malaria parasite Plasmodium falciparum is entering a new era with the arrival of site-specific genome engineering. Previously restricted only to model systems but now expanded to most laboratory organisms, and even to humans for experimental gene therapy studies, this technology allows researchers to rapidly generate previously unattainable genetic modifications. This technological advance is dependent on DNA double-strand break repair (DSBR), specifically homologous recombination in the case of Plasmodium. Our understanding of DSBR in malaria parasites, however, is based largely on assumptions and knowledge taken from other model systems, which do not always hold true in Plasmodium. Here we describe the causes of double-strand breaks, the mechanisms of DSBR, and the differences between model systems and P. falciparum. These mechanisms drive basic parasite functions, such as meiosis, antigen diversification, and copy number variation, and allow the parasite to continually evolve in the contexts of host immune pressure and drug selection. Finally, we discuss the new technologies that leverage DSBR mechanisms to accelerate genetic investigations into this global infectious pathogen. PMID:25184562

  15. DNA repair mechanisms and their biological roles in the malaria parasite Plasmodium falciparum.

    Science.gov (United States)

    Lee, Andrew H; Symington, Lorraine S; Fidock, David A

    2014-09-01

    Research into the complex genetic underpinnings of the malaria parasite Plasmodium falciparum is entering a new era with the arrival of site-specific genome engineering. Previously restricted only to model systems but now expanded to most laboratory organisms, and even to humans for experimental gene therapy studies, this technology allows researchers to rapidly generate previously unattainable genetic modifications. This technological advance is dependent on DNA double-strand break repair (DSBR), specifically homologous recombination in the case of Plasmodium. Our understanding of DSBR in malaria parasites, however, is based largely on assumptions and knowledge taken from other model systems, which do not always hold true in Plasmodium. Here we describe the causes of double-strand breaks, the mechanisms of DSBR, and the differences between model systems and P. falciparum. These mechanisms drive basic parasite functions, such as meiosis, antigen diversification, and copy number variation, and allow the parasite to continually evolve in the contexts of host immune pressure and drug selection. Finally, we discuss the new technologies that leverage DSBR mechanisms to accelerate genetic investigations into this global infectious pathogen.

  16. [The first monkey malaria in Turkey: a case of Plasmodium knowlesi].

    Science.gov (United States)

    Özbilgin, Ahmet; Çavuş, İbrahim; Yıldırım, Ahmet; Gündüz, Cumhur

    2016-07-01

    Plasmodium knowlesi is now added to the known four Plasmodium species (P.vivax, P.falciparum, P.malariae, P.ovale) as a cause of malaria in humans because of the recent increasing rate of cases reported from countries of southeastern Asia. P.knowlesi which infects macaque monkeys (Macaca fascicularis and M.nemestrina) is transmitted to humans especially by Anopheles leucosphyrus and An.hackeri mosquitos. First human cases of P.knowlesi malaria have been detected in Malaysia which have reached high numbers in recent years and also have been reported from countries of Southeast Asia such as Thailand, Philippines, Myanmar, Singapore and Vietnam. However the number of cases reported from western countries are rare and limited only within voyagers. This report is the first presentation of an imported case of P.knowlesi malaria in Turkey and aims to draw attention to the point that it could also be detected in future. A 33-year-old male patient from Myanmar who has migrated to Turkey as a refugee, was admitted to a health center with the complaints of fever with a periodicity of 24 hours, headache, fatigue, cough, sore throat, anorexia, myalgia and arthralgia. He was prediagnosed as upper respiratory tract infection, however because of his periodical fever and background in Myanmar, thick and thin blood films were prepared and sent to our laboratory for further examinations. Microscopic examination of the thin blood films revealed erythrocytic stages compatible with P.knowlesi (three large early trophozoites in an erythrocyte, three late trophozoites with compact view, and three late band-form trophozoites). Upon this, both real-time polymerase chain reaction (Rt-PCR) targeting the small subunit ribosomal RNA (SSU-rRNA) genes of Plasmodium genus and DNA sequence analysis targeting P.knowlesi rRNA gene were performed. As a result, the suspected identification of P.knowlesi by microscopy was confirmed by Rt-PCR and DNA sequencing. The patient was treated with chloroquine

  17. Thrombocytopenia in Plasmodium vivax malaria is related to platelets phagocytosis.

    Directory of Open Access Journals (Sweden)

    Helena Cristina C Coelho

    Full Text Available BACKGROUND: Although thrombocytopenia is a hematological disorder commonly reported in malarial patients, its mechanisms are still poorly understood, with only a few studies focusing on the role of platelets phagocytosis. METHODS AND FINDINGS: Thirty-five malaria vivax patients and eight healthy volunteers (HV were enrolled in the study. Among vivax malaria patients, thrombocytopenia (<150,000 platelets/µL was found in 62.9% (22/35. Mean platelet volume (MPV was higher in thrombocytopenic patients as compared to non-thrombocytopenic patients (p = 0.017 and a negative correlation was found between platelet count and MPV (r = -0.483; p = 0.003. Platelets from HV or patients were labeled with 5-chloromethyl fluorescein diacetate (CMFDA, incubated with human monocytic cell line (THP-1 and platelet phagocytosis index was analyzed by flow cytometry. The phagocytosis index was higher in thrombocytopenic patients compared to non-thrombocytopenic patients (p = 0.042 and HV (p = 0.048. A negative correlation was observed between platelet count and phagocytosis index (r = -0.402; p = 0.016. Platelet activation was assessed measuring the expression of P-selectin (CD62-P in platelets' surface by flow cytometry. No significant difference was found in the expression of P-selectin between thrombocytopenic patients and HV (p = 0.092. After evaluating the cytokine profile (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ and IL-17 in the patients' sera, levels of IL-6, IL-10 and IFN-γ were elevated in malaria patients compared to HV. Moreover, IL-6 and IL-10 values were higher in thrombocytopenic patients than non-thrombocytopenic ones (p = 0.044 and p = 0.017, respectively. In contrast, TNF-α levels were not different between the three groups, but a positive correlation was found between TNF-α and phagocytosis index (r = -0.305; p = 0.037. CONCLUSION/SIGNIFICANCE: Collectively, our findings indicate that platelet

  18. Muerte materna por malaria grave por Plasmodium vivax

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    Nancy Arróspide

    Full Text Available Se presenta el caso de una mujer de 19 años con 29 semanas de gestación, procedente de Llumpe (Ancash con antecedentes de viajes a las localidades de Chanchamayo (Junín y Rinconada (Ancash. Ingresó al Hospital de Chacas (Ancash por presentar mal estado general, deshidratación, dificultad respiratoria, ictericia, sensación de alza térmica y dolor abdominal, tuvo reporte de: hemoparásitos 60% en frotis sanguíneo. Fue transferida al Hospital Ramos Guardia (Huaraz donde presentó mayor dificultad respiratoria, coluria, hematuria, disminución del débito urinario y reporte de Plasmodium (+, luego fue transferida al Hospital Cayetano Heredia (Lima donde ingresó a la Unidad de Cuidados Intensivos (UCI, con evolución a falla multiorgánica, óbito fetal y muerte materna. Se confirmó infección por Plasmodium vivax. Destacamos la importancia de mejorar nuestras capacidades de diagnóstico y manejo para brindar un tratamiento adecuado y oportuno.

  19. [Maternal death from severe malaria due to Plasmodium vivax].

    Science.gov (United States)

    Arróspide, Nancy; Espinoza, Máximo Manuel; Miranda-Choque, Edwin; Mayta-Tristán, Percy; Legua, Pedro; Cabezas, César

    2016-06-01

    Here we describe the case of a 19-year-old woman, in her 29th week of gestation, who was from Llumpe (Ancash, Peru) and had a history of traveling to Chanchamayo (Junín, Peru) and Rinconada (Ancash, Peru). The patient presented at Chacas Hospital (Chacas, Ancash, Peru) with general malaise, dehydration, respiratory distress, jaundice, the sensation of thermal rise, and abdominal pain. Analysis of blood smears revealed 60% hemoparasites. She was transferred to Ramos Guardia Hospital (Huaraz, Peru) where she presented increasing respiratory distress, choluria, hematuria, and decreased urine output, moreover she was positive for Plasmodium. From there she was transferred to Cayetano Heredia Hospital (Lima, Peru), where she was admitted to the intensive care unit (ICU) with multiple organ failure, stillbirth, and leading to death. She underwent mechanical ventilation, was administered clindamycin, and was prescribed quinine, which she did not received due a lack by availability. The evolution of the illness was torpid, and she ultimately developed multiple organ failure and died. Plasmodium vivax infection was confirmed. Accordingly, we emphasize the importance of improving our diagnostic capabilities and management techniques to enable clinicians to provide adequate and timely treatment.

  20. Disease progression in Plasmodium knowlesi malaria is linked to variation in invasion gene family members.

    Directory of Open Access Journals (Sweden)

    Atique M Ahmed

    2014-08-01

    Full Text Available Emerging pathogens undermine initiatives to control the global health impact of infectious diseases. Zoonotic malaria is no exception. Plasmodium knowlesi, a malaria parasite of Southeast Asian macaques, has entered the human population. P. knowlesi, like Plasmodium falciparum, can reach high parasitaemia in human infections, and the World Health Organization guidelines for severe malaria list hyperparasitaemia among the measures of severe malaria in both infections. Not all patients with P. knowlesi infections develop hyperparasitaemia, and it is important to determine why. Between isolate variability in erythrocyte invasion, efficiency seems key. Here we investigate the idea that particular alleles of two P. knowlesi erythrocyte invasion genes, P. knowlesi normocyte binding protein Pknbpxa and Pknbpxb, influence parasitaemia and human disease progression. Pknbpxa and Pknbpxb reference DNA sequences were generated from five geographically and temporally distinct P. knowlesi patient isolates. Polymorphic regions of each gene (approximately 800 bp were identified by haplotyping 147 patient isolates at each locus. Parasitaemia in the study cohort was associated with markers of disease severity including liver and renal dysfunction, haemoglobin, platelets and lactate, (r = ≥ 0.34, p =  <0.0001 for all. Seventy-five and 51 Pknbpxa and Pknbpxb haplotypes were resolved in 138 (94% and 134 (92% patient isolates respectively. The haplotypes formed twelve Pknbpxa and two Pknbpxb allelic groups. Patients infected with parasites with particular Pknbpxa and Pknbpxb alleles within the groups had significantly higher parasitaemia and other markers of disease severity. Our study strongly suggests that P. knowlesi invasion gene variants contribute to parasite virulence. We focused on two invasion genes, and we anticipate that additional virulent loci will be identified in pathogen genome-wide studies. The multiple sustained entries of this diverse pathogen

  1. Disease progression in Plasmodium knowlesi malaria is linked to variation in invasion gene family members.

    Science.gov (United States)

    Ahmed, Atique M; Pinheiro, Miguel M; Divis, Paul C; Siner, Angela; Zainudin, Ramlah; Wong, Ing Tien; Lu, Chan Woon; Singh-Khaira, Sarina K; Millar, Scott B; Lynch, Sean; Willmann, Matthias; Singh, Balbir; Krishna, Sanjeev; Cox-Singh, Janet

    2014-08-01

    Emerging pathogens undermine initiatives to control the global health impact of infectious diseases. Zoonotic malaria is no exception. Plasmodium knowlesi, a malaria parasite of Southeast Asian macaques, has entered the human population. P. knowlesi, like Plasmodium falciparum, can reach high parasitaemia in human infections, and the World Health Organization guidelines for severe malaria list hyperparasitaemia among the measures of severe malaria in both infections. Not all patients with P. knowlesi infections develop hyperparasitaemia, and it is important to determine why. Between isolate variability in erythrocyte invasion, efficiency seems key. Here we investigate the idea that particular alleles of two P. knowlesi erythrocyte invasion genes, P. knowlesi normocyte binding protein Pknbpxa and Pknbpxb, influence parasitaemia and human disease progression. Pknbpxa and Pknbpxb reference DNA sequences were generated from five geographically and temporally distinct P. knowlesi patient isolates. Polymorphic regions of each gene (approximately 800 bp) were identified by haplotyping 147 patient isolates at each locus. Parasitaemia in the study cohort was associated with markers of disease severity including liver and renal dysfunction, haemoglobin, platelets and lactate, (r = ≥ 0.34, p =  <0.0001 for all). Seventy-five and 51 Pknbpxa and Pknbpxb haplotypes were resolved in 138 (94%) and 134 (92%) patient isolates respectively. The haplotypes formed twelve Pknbpxa and two Pknbpxb allelic groups. Patients infected with parasites with particular Pknbpxa and Pknbpxb alleles within the groups had significantly higher parasitaemia and other markers of disease severity. Our study strongly suggests that P. knowlesi invasion gene variants contribute to parasite virulence. We focused on two invasion genes, and we anticipate that additional virulent loci will be identified in pathogen genome-wide studies. The multiple sustained entries of this diverse pathogen into the human

  2. Fingerprinting the substrate specificity of M1 and M17 aminopeptidases of human malaria, Plasmodium falciparum.

    Directory of Open Access Journals (Sweden)

    Marcin Poreba

    Full Text Available BACKGROUND: Plasmodium falciparum, the causative agent of human malaria, expresses two aminopeptidases, PfM1AAP and PfM17LAP, critical to generating a free amino acid pool used by the intraerythrocytic stage of the parasite for proteins synthesis, growth and development. These exopeptidases are potential targets for the development of a new class of anti-malaria drugs. METHODOLOGY/PRINCIPAL FINDINGS: To define the substrate specificity of recombinant forms of these two malaria aminopeptidases we used a new library consisting of 61 fluorogenic substrates derived both from natural and unnatural amino acids. We obtained a detailed substrate fingerprint for recombinant forms of the enzymes revealing that PfM1AAP exhibits a very broad substrate tolerance, capable of efficiently hydrolyzing neutral and basic amino acids, while PfM17LAP has narrower substrate specificity and preferentially cleaves bulky, hydrophobic amino acids. The substrate library was also exploited to profile the activity of the native aminopeptidases in soluble cell lysates of P. falciparum malaria. CONCLUSIONS/SIGNIFICANCE: This data showed that PfM1AAP and PfM17LAP are responsible for majority of the aminopeptidase activity in these extracts. These studies provide specific substrate and mechanistic information important for understanding the function of these aminopeptidases and could be exploited in the design of new inhibitors to specifically target these for anti-malaria treatment.

  3. Fingerprinting the Substrate Specificity of M1 and M17 Aminopeptidases of Human Malaria, Plasmodium falciparum

    Science.gov (United States)

    Poreba, Marcin; McGowan, Sheena; Skinner-Adams, Tina S.; Trenholme, Katharine R.; Gardiner, Donald L.; Whisstock, James C.; To, Joyce; Salvesen, Guy S.; Dalton, John P.; Drag, Marcin

    2012-01-01

    Background Plasmodium falciparum, the causative agent of human malaria, expresses two aminopeptidases, PfM1AAP and PfM17LAP, critical to generating a free amino acid pool used by the intraerythrocytic stage of the parasite for proteins synthesis, growth and development. These exopeptidases are potential targets for the development of a new class of anti-malaria drugs. Methodology/Principal Findings To define the substrate specificity of recombinant forms of these two malaria aminopeptidases we used a new library consisting of 61 fluorogenic substrates derived both from natural and unnatural amino acids. We obtained a detailed substrate fingerprint for recombinant forms of the enzymes revealing that PfM1AAP exhibits a very broad substrate tolerance, capable of efficiently hydrolyzing neutral and basic amino acids, while PfM17LAP has narrower substrate specificity and preferentially cleaves bulky, hydrophobic amino acids. The substrate library was also exploited to profile the activity of the native aminopeptidases in soluble cell lysates of P. falciparum malaria. Conclusions/Significance This data showed that PfM1AAP and PfM17LAP are responsible for majority of the aminopeptidase activity in these extracts. These studies provide specific substrate and mechanistic information important for understanding the function of these aminopeptidases and could be exploited in the design of new inhibitors to specifically target these for anti-malaria treatment. PMID:22359643

  4. Efficacy of artemether-lumefantrine as a treatment for uncomplicated Plasmodium vivax malaria in eastern Sudan

    Directory of Open Access Journals (Sweden)

    Abdallah Tajeldin M

    2012-12-01

    Full Text Available Abstract Background Artemisinin-based combination therapy (ACT is the treatment of choice for uncomplicated Plasmodium falciparum malaria in most areas of the world, where malaria is endemic, including Sudan. However, few published data are available on the use of ACT for treatment of P. vivax malaria. Methods This study was conducted at a health centre in Kassala, eastern Sudan, from October to December 2011. Patients with uncomplicated P. vivax malaria received artemether-lumefantrine (AL tablets (containing 20mg artemether and 120 mg lumefantrine and were monitored for 28 days. Results Out of the 43 cases enrolled in this study, 38 completed the 28-day follow-up. Their mean age was 25.1 years (SD: 1.5. On day 3 following AL treatment, all of the patients were afebrile and aparasitaemic. By day 28, all 38 patients exhibited adequate clinical and parasitological responses to AL treatment. The cure rate was 100% and 88.4% for the per protocol analysis andfor the intention to treat analysis, respectively. Mild adverse effects (nausea, vomiting, abdominal pain, dizziness and/or rash that resolved spontaneously were observed in four (10.5% of the patients. Conclusion AL combination therapy was fully effective for treatment of P. vivax malaria in the study in eastern Sudan. Trial registration Trial. Gov: NCT01625871

  5. Endothelin-1 Mediates Brain Microvascular Dysfunction Leading to Long-Term Cognitive Impairment in a Model of Experimental Cerebral Malaria.

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    Brandi D Freeman

    2016-03-01

    Full Text Available Plasmodium falciparum infection causes a wide spectrum of diseases, including cerebral malaria, a potentially life-threatening encephalopathy. Vasculopathy is thought to contribute to cerebral malaria pathogenesis. The vasoactive compound endothelin-1, a key participant in many inflammatory processes, likely mediates vascular and cognitive dysfunctions in cerebral malaria. We previously demonstrated that C57BL6 mice infected with P. berghei ANKA, our fatal experimental cerebral malaria model, sustained memory loss. Herein, we demonstrate that an endothelin type A receptor (ETA antagonist prevented experimental cerebral malaria-induced neurocognitive impairments and improved survival. ETA antagonism prevented blood-brain barrier disruption and cerebral vasoconstriction during experimental cerebral malaria, and reduced brain endothelial activation, diminishing brain microvascular congestion. Furthermore, exogenous endothelin-1 administration to P. berghei NK65-infected mice, a model generally regarded as a non-cerebral malaria negative control for P. berghei ANKA infection, led to experimental cerebral malaria-like memory deficits. Our data indicate that endothelin-1 is critical in the development of cerebrovascular and cognitive impairments with experimental cerebral malaria. This vasoactive peptide may thus serve as a potential target for adjunctive therapy in the management of cerebral malaria.

  6. Endothelin-1 Mediates Brain Microvascular Dysfunction Leading to Long-Term Cognitive Impairment in a Model of Experimental Cerebral Malaria.

    Directory of Open Access Journals (Sweden)

    Brandi D Freeman

    2016-03-01

    Full Text Available Plasmodium falciparum infection causes a wide spectrum of diseases, including cerebral malaria, a potentially life-threatening encephalopathy. Vasculopathy is thought to contribute to cerebral malaria pathogenesis. The vasoactive compound endothelin-1, a key participant in many inflammatory processes, likely mediates vascular and cognitive dysfunctions in cerebral malaria. We previously demonstrated that C57BL6 mice infected with P. berghei ANKA, our fatal experimental cerebral malaria model, sustained memory loss. Herein, we demonstrate that an endothelin type A receptor (ETA antagonist prevented experimental cerebral malaria-induced neurocognitive impairments and improved survival. ETA antagonism prevented blood-brain barrier disruption and cerebral vasoconstriction during experimental cerebral malaria, and reduced brain endothelial activation, diminishing brain microvascular congestion. Furthermore, exogenous endothelin-1 administration to P. berghei NK65-infected mice, a model generally regarded as a non-cerebral malaria negative control for P. berghei ANKA infection, led to experimental cerebral malaria-like memory deficits. Our data indicate that endothelin-1 is critical in the development of cerebrovascular and cognitive impairments with experimental cerebral malaria. This vasoactive peptide may thus serve as a potential target for adjunctive therapy in the management of cerebral malaria.

  7. Global histone analysis by mass spectrometry reveals a high content of acetylated lysine residues in the malaria parasite Plasmodium falciparum

    DEFF Research Database (Denmark)

    Trelle, Morten Beck; Salcedo-Amaya, Adriana M; Cohen, Adrian

    2009-01-01

    Post-translational modifications (PTMs) of histone tails play a key role in epigenetic regulation of gene expression in a range of organisms from yeast to human, however, little is known about histone proteins from the parasite that causes malaria in humans, Plasmodium falciparum. We characterize...... comprehensive map of histone modifications in Plasmodium falciparum and highlight the utility of tandem MS for detailed analysis of peptides containing multiple PTMs....

  8. Non-falciparum malaria in Dakar: a confirmed case of Plasmodium ovale wallikeri infection.

    Science.gov (United States)

    Diallo, Mamadou A; Badiane, Aida S; Diongue, Khadim; Deme, Awa; Lucchi, Naomi W; Gaye, Marie; Ndiaye, Tolla; Ndiaye, Mouhamadou; Sene, Louise K; Diop, Abdoulaye; Gaye, Amy; Ndiaye, Yaye D; Samb, Diama; Yade, Mamadou S; Ndir, Omar; Udhayakumar, Venkatachalam; Ndiaye, Daouda

    2016-08-24

    Plasmodium ovale is rarely described in Senegal. A case of clinical malaria due to P. ovale wallikeri in West Central of Senegal is reported. A 34-year-old male baker in Dakar, with no significant previous medical history, was admitted to a health clinic with fever and vomiting. Fever had been lasting for 4 days with peaks every 48 h. As monospecific Plasmodium falciparum HRP-2 RDT was negative, he was treated with antibiotics. However, owing to persisting symptoms, he was referred to the emergency unit of the Youssou Mbargane Diop Hospital, Dakar, Senegal. Clinical examination found impaired general condition. All other physical examinations were normal. Laboratory tests showed anaemia (haemoglobin 11.4 g/dl), severe thrombocytopaenia (platelets 30 × 10(9)/mm(3)), leukopenia (3650/mm(3)), lymphocytopenia (650/mm(3)). Renal function was normal as indicated by creatininaemia and uraemia (11 mg/l and 0.25 g/l, respectively) and liver enzymes were slightly elevated (aspartate aminotransferase 77 UI/l and alanine aminotransferase 82 UI/l). Blood smear evaluations in Parasitology Laboratory of Aristide Le Dantec Hospital showed malaria parasites of the species P. ovale with a 0.08 % parasitaemia. Molecular confirmation was done by real time PCR targeting the 18S rRNA gene. The P. ovale infection was further analysed to species level targeting the potra gene and was identified as P. ovale wallikeri. According to the hospital's malaria treatment guidelines for severe malaria, treatment consisted of intravenous quinine at hour 0 (start of treatment) and 24 h after initial treatment, followed by artemether-lumefantrine 24 h later. A negative microscopy was noted on day 3 post-treatment and the patient reported no further symptoms. Malaria due to non-falciparum species is probably underestimated in Senegal. RDTs specific to non-falciparum species and/or pan specific RDTs should be included as tools of diagnosis to fight against malaria in Senegal. In addition

  9. A potential role for plasma uric acid in the endothelial pathology of Plasmodium falciparum malaria.

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    Neida K Mita-Mendoza

    Full Text Available BACKGROUND: Inflammatory cytokinemia and systemic activation of the microvascular endothelium are central to the pathogenesis of Plasmodium falciparum malaria. Recently, 'parasite-derived' uric acid (UA was shown to activate human immune cells in vitro, and plasma UA levels were associated with inflammatory cytokine levels and disease severity in Malian children with malaria. Since UA is associated with endothelial inflammation in non-malaria diseases, we hypothesized that elevated UA levels contribute to the endothelial pathology of P. falciparum malaria. METHODOLOGY/PRINCIPAL FINDINGS: We measured levels of UA and soluble forms of intercellular adhesion molecule-1 (sICAM-1, vascular cell adhesion molecule-1 (sVCAM-1, E-selectin (sE-Selectin, thrombomodulin (sTM, tissue factor (sTF and vascular endothelial growth factor (VEGF in the plasma of Malian children aged 0.5-17 years with uncomplicated malaria (UM, n = 487 and non-cerebral severe malaria (NCSM, n = 68. In 69 of these children, we measured these same factors once when they experienced a malaria episode and twice when they were healthy (i.e., before and after the malaria transmission season. We found that levels of UA, sICAM-1, sVCAM-1, sE-Selectin and sTM increase during a malaria episode and return to basal levels at the end of the transmission season (p<0.0001. Plasma levels of UA and these four endothelial biomarkers correlate with parasite density and disease severity. In children with UM, UA levels correlate with parasite density (r = 0.092, p = 0.043, sICAM-1 (r = 0.255, p<0.0001 and sTM (r = 0.175, p = 0.0001 levels. After adjusting for parasite density, UA levels predict sTM levels. CONCLUSIONS/SIGNIFICANCE: Elevated UA levels may contribute to malaria pathogenesis by damaging endothelium and promoting a procoagulant state. The correlation between UA levels and parasite densities suggests that parasitized erythrocytes are one possible source of excess UA. UA-induced shedding of

  10. A potential role for plasma uric acid in the endothelial pathology of Plasmodium falciparum malaria.

    Science.gov (United States)

    Mita-Mendoza, Neida K; van de Hoef, Diana L; Lopera-Mesa, Tatiana M; Doumbia, Saibou; Konate, Drissa; Doumbouya, Mory; Gu, Wenjuan; Anderson, Jennifer M; Santos-Argumedo, Leopoldo; Rodriguez, Ana; Fay, Michael P; Diakite, Mahamadou; Long, Carole A; Fairhurst, Rick M

    2013-01-01

    Inflammatory cytokinemia and systemic activation of the microvascular endothelium are central to the pathogenesis of Plasmodium falciparum malaria. Recently, 'parasite-derived' uric acid (UA) was shown to activate human immune cells in vitro, and plasma UA levels were associated with inflammatory cytokine levels and disease severity in Malian children with malaria. Since UA is associated with endothelial inflammation in non-malaria diseases, we hypothesized that elevated UA levels contribute to the endothelial pathology of P. falciparum malaria. We measured levels of UA and soluble forms of intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-Selectin), thrombomodulin (sTM), tissue factor (sTF) and vascular endothelial growth factor (VEGF) in the plasma of Malian children aged 0.5-17 years with uncomplicated malaria (UM, n = 487) and non-cerebral severe malaria (NCSM, n = 68). In 69 of these children, we measured these same factors once when they experienced a malaria episode and twice when they were healthy (i.e., before and after the malaria transmission season). We found that levels of UA, sICAM-1, sVCAM-1, sE-Selectin and sTM increase during a malaria episode and return to basal levels at the end of the transmission season (p<0.0001). Plasma levels of UA and these four endothelial biomarkers correlate with parasite density and disease severity. In children with UM, UA levels correlate with parasite density (r = 0.092, p = 0.043), sICAM-1 (r = 0.255, p<0.0001) and sTM (r = 0.175, p = 0.0001) levels. After adjusting for parasite density, UA levels predict sTM levels. Elevated UA levels may contribute to malaria pathogenesis by damaging endothelium and promoting a procoagulant state. The correlation between UA levels and parasite densities suggests that parasitized erythrocytes are one possible source of excess UA. UA-induced shedding of endothelial TM may represent a novel mechanism of malaria pathogenesis, in

  11. 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.

  12. Plasmodium vivax sporozoite challenge in malaria-naive and semi-immune Colombian volunteers.

    Directory of Open Access Journals (Sweden)

    Myriam Arévalo-Herrera

    Full Text Available Significant progress has been recently achieved in the development of Plasmodium vivax challenge infections in humans, which are essential for vaccine and drug testing. With the goal of accelerating clinical development of malaria vaccines, the outcome of infections experimentally induced in naïve and semi-immune volunteers by infected mosquito bites was compared.Seven malaria-naïve and nine semi-immune Colombian adults (n = 16 were subjected to the bites of 2-4 P. vivax sporozoite-infected Anopheles mosquitoes. Parasitemia levels, malaria clinical manifestations, and immune responses were assessed and compared.All volunteers developed infections as confirmed by microscopy and RT-qPCR. No significant difference in the pre-patent period (mean 12.5 and 12.8 days for malaria-naïve and malaria-exposed, respectively was observed but naïve volunteers developed classical malaria signs and symptoms, while semi-immune volunteers displayed minor or no symptoms at the day of diagnosis. A malaria-naïve volunteer developed a transient low submicroscopic parasitemia that cured spontaneously. Infection induced an increase in specific antibody levels in both groups.Sporozoite infectious challenge was safe and reproducible in semi-immune and naïve volunteers. This model will provide information for simultaneous comparison of the protective efficacy of P. vivax vaccines in naïve and semi-immune volunteers under controlled conditions and would accelerate P. vivax vaccine development.clinicaltrials.gov NCT01585077.

  13. Augmented particle trapping and attenuated inflammation in the liver by protective vaccination against Plasmodium chabaudi malaria

    Directory of Open Access Journals (Sweden)

    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.

  14. Optimization of an in vitro system to study the exo-erythrocytic stage of the human malaria parasite, Plasmodium falciparum

    CSIR Research Space (South Africa)

    Rossouw, C

    2010-02-01

    Full Text Available scaffold and harvesting cells via the temperature change is currently being scaled up and a prototype bioreactor has been developed. Optimization of an in vitro system to study the exo-erythrocytic stage of the human Malaria Parasite, Plasmodium... hepatocyte line that supports in vitro development of the exo-erythrocytic stages of the malaria parasites Plasmodium falciparum and P. vivax. American Journal of Tropical Medicine and Hygeine 74:708-715. [4] Shor L, Güçeri S, Wen X, Gandhi M, Sun W. 2007...

  15. Kinetics of B Cell responses to Plasmodium falciparum erythrocyte membrane protein 1 in Ghanaian women naturally exposed to malaria parasites

    DEFF Research Database (Denmark)

    Ampomah, Paulina; Stevenson, Liz; Ofori, Michael F

    2014-01-01

    Naturally acquired protective immunity to Plasmodium falciparum malaria takes years to develop. It relies mainly on Abs, particularly IgG specific for Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) proteins on the infected erythrocyte surface. It is only partially understood why...... confirmed earlier reports of high atypical memory B cell frequencies among residents of P. falciparum-endemic areas, and indicated an additional effect of pregnancy. Our study provides new knowledge regarding immunity to P. falciparum malaria and underpins efforts to develop PfEMP1-based vaccines against...

  16. 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.

  17. Comparing histopathology of ICR mice infected with chloroquine-sensitive and chloroquine-resistant strains of Plasmodium berghei%伯氏疟原虫氯喹敏感株和抗性株感染ICR鼠病理变化的比较研究

    Institute of Scientific and Technical Information of China (English)

    陈克强; 宋关鸿

    2001-01-01

    目的:研究伯氏疟原虫(Plasmodium berghei)的抗药性与致病力的关系。方法:比较伯氏疟原虫氯喹敏感株(N)和抗性株(RC)感染ICR鼠的肝、脾、脑、心、肺、肾等重要脏器病理组织学的动态变化。结果:N株感染后,小鼠肝、脾有较多的疟色素沉着,肺脏呈郁血性水肿;脑微血管充血和阻塞;各脏器呈急性炎症的病理变化特点。RC株感染后,小鼠肝、脾脏的病理组织学改变与原虫血症的变化有关。肺脏呈间质性肺炎,各脏器呈慢性增生性炎症的病理变化特点。结论:N株致病力较强,感染后引起宿主死亡的主要原因是感染疟原虫的红细胞对脑微血管内皮细胞的粘附,造成微血管阻塞;RC株致病力较弱,宿主的应答反应在感染早期可能是CD4+Th1相关的迟发型超敏炎症反应,而感染后期是CD4+T h2辅助作用下的抗体依赖性的免疫应答,并在疟原虫的最后清除上起着关键性的作用。%Objective: To understand the relationship between chloroquine resistance and the virulence of Plasmodium berghei. Met hods: Dynamic changes of histopathologic features of livers, spleens, brains, hearts, lungs and kidneys of mice infected with the chloroquine-sensitive (N) and the chloroquine-resistant (RC) strains of P. berghei were compared. Results: In mice infected with the N strain, deposition of heavy hemoz oin in livers and spleens, congestive edema in lungs, and congestion and embolis m in the brain capillaries were observed. The histopathologic features revealed ac ute inflammatory reaction. In mice infected with the RC strain, histopathologic variations of livers and spleens were associated with changes of parasitemia. In terstitial pneumonia was displayed in lungs. There were chronic histopathologic changes of the organs in the mice infected with RC strain. Conclusion: The mice infected by the N strain with potent virulence die due to adher ence of

  18. Paludismo por Plasmodium falciparum adquirido en África subsahariana Plasmodium falciparum malaria acquired in Subsaharian Africa

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    Ricardo Durlach

    2009-02-01

    Full Text Available El objetivo de este trabajo es presentar los casos de paludismo por Plasmodium falciparum ocurridos en viajeros provenientes del África tropical, atendidos en el Hospital Alemán. Se definió paludismo de origen africano como la infección adquirida en un país del África subsahariana, diagnosticado y tratado en la Argentina. El diagnóstico se realizó por la clínica y la microscopía óptica en frotis de sangre periférica coloreados con Giemsa. Se revieron las historias clínicas de 11 pacientes adultos -cinco turistas y seis marineros mercantes- no oriundos de área endémica, sin condición inmunosupresora, ni morbilidad asociada, internados entre 1993 y 2007. El rango de edad fue de 21 a 48 años; nueve hombres y dos mujeres. Los pacientes fueron clasificados retrospectivamente en malaria grave (seis o no grave (cinco según cumplieran con uno o más de los criterios de gravedad de la Organización Mundial de la Salud. Todos presentaron fiebre como signo más significativo. Como complicaciones graves se observaron casos de insuficiencia renal, epistaxis, hemoglobinuria, hipoglucemia, edema pulmonar, acidosis y coma. Tres pacientes requirieron internación en la unidad de terapia intensiva. Todos sobrevivieron y solamente tres habían recibido la quimioprofilaxis correcta antes de viajar. El tratamiento se realizó con una o más de las siguientes drogas: mefloquina, quinidina, clindamicina y cotrimoxazol.The purpose of this paper is to present the cases of malaria caused by Plasmodium falciparum in travelers coming from tropical Africa, who were treated at the Hospital Alemán (Buenos Aires. African malaria was defined as an infection acquired in any country within Africa, diagnosed and treated in Argentina. Diagnostic tools included clinical features and optic microscopy with Giemsa stained peripheral blood films. We reviewed the medical records of 11 adult patients -five tourists and six sailors- with no history of malaria

  19. Core genome components and lineage specific expansions in malaria parasites Plasmodium

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    Gu Jianying

    2010-12-01

    Full Text Available Abstract Background The increasing resistance of Plasmodium, the malaria parasites, to multiple commonly used drugs has underscored the urgent need to develop effective antimalarial drugs and vaccines. The new direction of genomics-driven target discovery has become possible with the completion of parasite genome sequencing, which can lead us to a better understanding of how the parasites develop the genetic variability that is associated with their response to environmental challenges and other adaptive phenotypes. Results We present the results of a comprehensive analysis of the genomes of six Plasmodium species, including two species that infect humans, one that infects monkeys, and three that infect rodents. The core genome shared by all six species is composed of 3,351 genes, which make up about 22%-65% of the genome repertoire. These components play important roles in fundamental functions as well as in parasite-specific activities. We further investigated the distribution and features of genes that have been expanded in specific Plasmodium lineage(s. Abundant duplicate genes are present in the six species, with 5%-9% of the whole genomes composed lineage specific radiations. The majority of these gene families are hypothetical proteins with unknown functions; a few may have predicted roles such as antigenic variation. Conclusions The core genome components in the malaria parasites have functions ranging from fundamental biological processes to roles in the complex networks that sustain the parasite-specific lifestyles appropriate to different hosts. They represent the minimum requirement to maintain a successful life cycle that spans vertebrate hosts and mosquito vectors. Lineage specific expansions (LSEs have given rise to abundant gene families in Plasmodium. Although the functions of most families remain unknown, these LSEs could reveal components in parasite networks that, by their enhanced genetic variability, can contribute to

  20. Further antiplasmodial effects of the aqueous extract of cym-bopogon citratus stapf (lemon grass) against plasmodium berghei in Swiss albino mice

    Institute of Scientific and Technical Information of China (English)

    DV Dapper; IMSiminialayi; OO Ebong

    2008-01-01

    Lemon grass (Cymbopogon citratus Stapf)is a popular alternative to western medicines for a number of condi-tions,including fevers,muscle soreness and superficial infections in Nigeria.In addition to its already reported suppressive effects against P.berghei infection,this study sought to determine its repository and blood schizon-ticidal activities in established P.berghei infection using Swiss albino mice as models.Mice weighing on aver-age,between 15 and 25g were given 103mg/kg,155mg/kg and 310mg/kg/day of the crude aqueous extract of cymbopogon citratus stapf,in the 4-day test,24-hour Rane test and 72-hour Rane test.The effects of these do-ses of the extract were then compared with chloroquine (5mg/kg/day)and sulphadoxine /pyrimethamine (3mg/kg/day).We report an average percentage suppressive repository activity of 65.8% for the extract at a dose of 310mg/kg and a blood schizonticidal activity that increased from 68.33% in the 24-hour Rane test to 92% in the 72-hour Rane test for the same dose of extract.The crude aqueous extract of C.citratus stapf thus has significant repository and blood schizonticidal activities against established P.berghei infection in Swiss al-bino mice compare to that of pyrimethamine and sulphadoxine /pyrimethamine respectively.

  1. Plasmodium falciparum Malaria: Band 3 as a Possible Receptor during Invasion of Human Erythrocytes

    Science.gov (United States)

    Okoye, Vincent C. N.; Bennett, Vann

    1985-01-01

    Human erythrocyte band 3, a major membrane-spanning protein, was purified and incorporated into liposomes. These liposomes, at nanomolar concentrations of protein, inhibited invasion of human erythrocytes in vitro by the malaria parasite Plasmodium falciparum. Liposomes containing human band 3 were ten times more effective in inhibiting invasion than those with pig band 3 and six times more effective than liposomes containing human erythrocyte glycophorin. Liposomes alone or liposomes containing erythrocyte glycolipids did not inhibit invasion. These results suggest that band 3 participates in the invasion process in a step involving a specific, high-affinity interaction between band 3 and some component of the parasite.

  2. Anti-Plasmodium falciparum invasion ligand antibodies in a low malaria transmission region, Loreto, Peru

    DEFF Research Database (Denmark)

    Villasis, Elizabeth; Lopez-Perez, Mary; Torres, Katherine

    2012-01-01

    , PfRh2a and PfRh2b and IgG3 response for PfRh2a were also negatively correlated with parasitaemia. Conclusions: These data suggest that falciparum malaria patients who develop clinical immunity (asymptomatic parasitaemia) in a low transmission setting such as the Peruvian Amazon have antibody......Background: Erythrocyte invasion by Plasmodium falciparum is a complex process that involves two families; Erythrocyte Binding-Like (EBL) and the Reticulocyte Binding-Like (PfRh) proteins. Antibodies that inhibit merozoite attachment and invasion are believed to be important in mediating naturally...

  3. Plasmodium falciparum malaria occurring four years after leaving an endemic area.

    Science.gov (United States)

    Vantomme, B; Van Acker, J; Rogge, S; Ommeslag, D; Donck, J; Callens, S

    2016-04-01

    We present a case of a 52-year-old woman of Ghanaian origin who developed Plasmodium falciparum malaria 4 years after leaving Africa. She had not returned to an endemic area since. We hypothesize several possible scenarios to explain this infection, of which we believe recrudescence of P. falciparum is the most plausible. This occurred most likely as a consequence of waning immunity several years after leaving a high-transmission area. She recovered after a 3-day treatment with atovaquone/proguanil.

  4. Malaria in pregnancy in rural Mozambique: the role of parity, submicroscopic and multiple Plasmodium falciparum infections.

    Science.gov (United States)

    Saute, Francisco; Menendez, Clara; Mayor, Alfredo; Aponte, John; Gomez-Olive, Xavier; Dgedge, Martinho; Alonso, Pedro

    2002-01-01

    Falciparum malaria affects pregnant women, especially primigravidae, but before malaria control programmes targeted to them can be designed, a description of the frequency and parity pattern of the infection is needed. There is little information on the frequency and effect of submicroscopic malaria infection, as well as on multiplicity of Plasmodium falciparum genotypes in pregnancy. This study aimed to describe the prevalence of malaria parasitaemia and anaemia and their relation to parity and age in pregnant women, during two malaria transmission seasons in a rural area of southern Mozambique. It also tried to assess the frequency and effect on anaemia of submicroscopic and multiple falciparum infections. A total of 686 pregnant women were enrolled in three cross-sectional community-based surveys during different transmission seasons in rural southern Mozambique. In each survey a questionnaire was administered on previous parity history, the gestational age was assessed, the axillary temperature recorded and both haematocrit and malaria parasitaemia were determined. We used polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis to determine submicroscopic and multiple P. falciparum infections in a subsample of women. A total of 156 women (23%) had microscopic parasitaemia, of which 144 (92%) were asexual forms of P. falciparum. The prevalence of clinical malaria was 18 of 534 (3%), that of anaemia, 382 of 649 (59%). In a multivariate analysis age but not parity was associated with an increased risk of microscopic parasitaemia. Anaemia was associated with microscopic P. falciparum parasitaemia. Both malaria parasitaemia and anaemia were more frequent during the rainy season. Although not statistically significant, submicroscopic infections tended to be more frequent among grand-multiparous pregnant women. Subpatent infections were not associated with increased anaemia. Multiplicity of infection was not associated with either

  5. A systematic review of the clinical presentation, treatment and relapse characteristics of human Plasmodium ovale malaria.

    Science.gov (United States)

    Groger, Mirjam; Fischer, Hannah S; Veletzky, Luzia; Lalremruata, Albert; Ramharter, Michael

    2017-03-11

    Despite increased efforts to control and ultimately eradicate human malaria, Plasmodium ovale malaria is for the most part outside the focus of research or public health programmes. Importantly, the understanding of P. ovale-nowadays regarded as the two distinct species P. ovale wallikeri and P. ovale curtisi-largely stems from case reports and case series lacking study designs providing high quality evidence. Consecutively, there is a lack of systematic evaluation of the clinical presentation, appropriate treatment and relapse characteristics of P. ovale malaria. The aim of this systematic review is to provide a systematic appraisal of the current evidence for severe manifestations, relapse characteristics and treatment options for human P. ovale malaria. This systematic review was performed according to the PRISMA guidelines and registered in the international prospective register for systematic reviews (PROSPERO 2016:CRD42016039214). P. ovale mono-infection was a strict inclusion criterion. Of 3454 articles identified by the literature search, 33 articles published between 1922 and 2015 met the inclusion criteria. These articles did not include randomized controlled trials. Five prospective uncontrolled clinical trials were performed on a total of 58 participants. P. ovale was sensitive to all tested drugs within the follow-up periods and on interpretable in vitro assays. Since its first description in 1922, only 18 relapsing cases of P. ovale with a total of 28 relapse events were identified in the scientific literature. There was however no molecular evidence for a causal relationship between dormant liver stages and subsequent relapses. A total of 22 severe cases of P. ovale malaria were published out of which five were fatal. Additionally, two cases of congenital P. ovale malaria were reported. Current knowledge of P. ovale malaria is based on small trials with minor impact, case reports and clinical observations. This systematic review highlights that P

  6. Genetic diversity and gene flow of humans, Plasmodium falciparum, and Anopheles farauti s.s. of Vanuatu: inferred malaria dispersal and implications for malaria control.

    Science.gov (United States)

    Lum, J K; Kaneko, A; Taleo, G; Amos, M; Reiff, D M

    2007-08-01

    A comparison of the patterns of gene flow within and between islands and the genetic diversities of the three species required for malaria transmission (humans, Plasmodium falciparum, and Anopheles farauti s.s.) within the model island system of Vanuatu, shows that the active dispersal of An. farauti s.s. is responsible for within island movement of parasites. In contrast, since both P. falciparum and An. farauti s.s. populations are largely restricted to islands, movement of parasites between islands is likely due to human transport. Thus, control of vectors is crucial for controlling malaria within islands, while control of human movement is essential to control malaria transmission across the archipelago.

  7. Plasmodium falciparum malaria in children aged 0-2 years: the role of foetal haemoglobin and maternal antibodies to two asexual malaria vaccine candidates (MSP3 and GLURP).

    Science.gov (United States)

    Kangoye, David Tiga; Nebie, Issa; Yaro, Jean-Baptiste; Debe, Siaka; Traore, Safiatou; Ouedraogo, Oumarou; Sanou, Guillaume; Soulama, Issiaka; Diarra, Amidou; Tiono, Alfred; Marsh, Kevin; Sirima, Sodiomon Bienvenu; Bejon, Philip

    2014-01-01

    Children below six months are reported to be less susceptible to clinical malaria. Maternally derived antibodies and foetal haemoglobin are important putative protective factors. We examined antibodies to Plasmodium falciparum merozoite surface protein 3 (MSP3) and glutamate-rich protein (GLURP), in children in their first two years of life in Burkina Faso and their risk of malaria. A cohort of 140 infants aged between four and six weeks was recruited in a stable transmission area of south-western Burkina Faso and monitored for 24 months by active and passive surveillance. Malaria infections were detected by examining blood smears using light microscopy. Enzyme-linked immunosorbent assay was used to quantify total Immunoglobulin G to Plasmodium falciparum antigens MSP3 and two regions of GLURP (R0 and R2) on blood samples collected at baseline, three, six, nine, 12, 18 and 24 months. Foetal haemoglobin and variant haemoglobin fractions were measured at the baseline visit using high pressure liquid chromatography. A total of 79.6% of children experienced one or more episodes of febrile malaria during monitoring. Antibody titres to MSP3 were prospectively associated with an increased risk of malaria while antibody responses to GLURP (R0 and R2) did not alter the risk. Antibody titres to MSP3 were higher among children in areas of high malaria risk. Foetal haemoglobin was associated with delayed first episode of febrile malaria and haemoglobin CC type was associated with reduced incidence of febrile malaria. We did not find any evidence of association between titres of antibodies to MSP3, GLURP-R0 or GLURP-R2 as measured by enzyme-linked immunosorbent assay and early protection against malaria, although anti-MSP3 antibody titres may reflect increased exposure to malaria and therefore greater risk. Foetal haemoglobin was associated with protection against febrile malaria despite the study limitations and its role is therefore worthy further investigation.

  8. Plasmodium falciparum malaria in children aged 0-2 years: the role of foetal haemoglobin and maternal antibodies to two asexual malaria vaccine candidates (MSP3 and GLURP.

    Directory of Open Access Journals (Sweden)

    David Tiga Kangoye

    Full Text Available Children below six months are reported to be less susceptible to clinical malaria. Maternally derived antibodies and foetal haemoglobin are important putative protective factors. We examined antibodies to Plasmodium falciparum merozoite surface protein 3 (MSP3 and glutamate-rich protein (GLURP, in children in their first two years of life in Burkina Faso and their risk of malaria.A cohort of 140 infants aged between four and six weeks was recruited in a stable transmission area of south-western Burkina Faso and monitored for 24 months by active and passive surveillance. Malaria infections were detected by examining blood smears using light microscopy. Enzyme-linked immunosorbent assay was used to quantify total Immunoglobulin G to Plasmodium falciparum antigens MSP3 and two regions of GLURP (R0 and R2 on blood samples collected at baseline, three, six, nine, 12, 18 and 24 months. Foetal haemoglobin and variant haemoglobin fractions were measured at the baseline visit using high pressure liquid chromatography.A total of 79.6% of children experienced one or more episodes of febrile malaria during monitoring. Antibody titres to MSP3 were prospectively associated with an increased risk of malaria while antibody responses to GLURP (R0 and R2 did not alter the risk. Antibody titres to MSP3 were higher among children in areas of high malaria risk. Foetal haemoglobin was associated with delayed first episode of febrile malaria and haemoglobin CC type was associated with reduced incidence of febrile malaria.We did not find any evidence of association between titres of antibodies to MSP3, GLURP-R0 or GLURP-R2 as measured by enzyme-linked immunosorbent assay and early protection against malaria, although anti-MSP3 antibody titres may reflect increased exposure to malaria and therefore greater risk. Foetal haemoglobin was associated with protection against febrile malaria despite the study limitations and its role is therefore worthy further investigation.

  9. Large-scale growth of the Plasmodium falciparum malaria parasite in a wave bioreactor.

    Science.gov (United States)

    Dalton, John P; Demanga, Corine G; Reiling, Sarah J; Wunderlich, Juliane; Eng, Jenny W L; Rohrbach, Petra

    2012-01-01

    We describe methods for the large-scale in vitro culturing of synchronous and asynchronous blood-stage Plasmodium falciparum parasites in sterile disposable plastic bioreactors controlled by wave-induced motion (wave bioreactor). These cultures perform better than static flask cultures in terms of preserving parasite cell cycle synchronicity and reducing the number of multiple-infected erythrocytes. The straight-forward methods described here will facilitate the large scale production of malaria parasites for antigen and organelle isolation and characterisation, for the high throughput screening of compound libraries with whole cells or extracts, and the development of live- or whole-cell malaria vaccines under good manufacturing practice compliant standards. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  10. Targeting of a Transporter to the Outer Apicoplast Membrane in the Human Malaria Parasite Plasmodium falciparum

    Science.gov (United States)

    Goodman, Christopher D.; McFadden, Geoffrey I.

    2016-01-01

    Apicoplasts are vestigial plastids in apicomplexan parasites like Plasmodium, the causative agent of malaria. Apicomplexan parasites are dependant on their apicoplasts for synthesis of various molecules that they are unable to scavenge in sufficient quantity from their host, which makes apicoplasts attractive drug targets. Proteins known as plastid phosphate translocators (pPTs) are embedded in the outer apicoplast membrane and are responsible for the import of carbon, energy and reducing power to drive anabolic synthesis in the organelle. We investigated how a pPT is targeted into the outer apicoplast membrane of the human malaria parasite P. falciparum. We showed that a transmembrane domain is likely to act as a recessed signal anchor to direct the protein into the endomembrane system, and that a tyrosine in the cytosolic N-terminus of the protein is essential for targeting, but one or more, as yet unidentified, factors are also essential to direct the protein into the outer apicoplast membrane. PMID:27442138

  11. What Is Known about the Immune Response Induced by Plasmodium vivax Malaria Vaccine Candidates?

    Science.gov (United States)

    López, Carolina; Yepes-Pérez, Yoelis; Hincapié-Escobar, Natalia; Díaz-Arévalo, Diana; Patarroyo, Manuel A.

    2017-01-01

    Malaria caused by Plasmodium vivax continues being one of the most important infectious diseases around the world; P. vivax is the second most prevalent species and has the greatest geographic distribution. Developing an effective antimalarial vaccine is considered a relevant control strategy in the search for means of preventing the disease. Studying parasite-expressed proteins, which are essential in host cell invasion, has led to identifying the regions recognized by individuals who are naturally exposed to infection. Furthermore, immunogenicity studies have revealed that such regions can trigger a robust immune response that can inhibit sporozoite (hepatic stage) or merozoite (erythrocyte stage) invasion of a host cell and induce protection. This review provides a synthesis of the most important studies to date concerning the antigenicity and immunogenicity of both synthetic peptide and recombinant protein candidates for a vaccine against malaria produced by P. vivax. PMID:28243235

  12. Plasmodium falciparum kelch 13: a potential molecular marker for tackling artemisinin-resistant malaria parasites.

    Science.gov (United States)

    Mita, Toshihiro; Tachibana, Shin-Ichiro; Hashimoto, Muneaki; Hirai, Makoto

    2016-01-01

    Although artemisinin combination therapies have been deployed as a first-line treatment for uncomplicated malaria in almost all endemic countries, artemisinin-resistant parasites have emerged and have gradually spread across the Greater Mekong subregions. There is growing concern that the resistant parasites may migrate to or emerge indigenously in sub-Saharan Africa, which might provoke a global increase in malaria-associated morbidity and mortality. Therefore, development of molecular markers that enable identification of artemisinin resistance with high sensitivity is urgently required to combat this issue. In 2014, a potential artemisinin-resistance responsible gene, Plasmodium falciparum kelch13, was discovered. Here, we review the genetic features of P. falciparum kelch13 and discuss its related resistant mechanisms and potential as a molecular marker.

  13. Gibberellin biosynthetic inhibitors make human malaria parasite Plasmodium falciparum cells swell and rupture to death.

    Directory of Open Access Journals (Sweden)

    Tomoko Toyama

    Full Text Available Malaria remains as one of the most devastating infectious disease, and continues to exact an enormous toll in medical cost and days of labor lost especially in the tropics. Effective malaria control and eventual eradication remain a huge challenge, with efficacious antimalarials as important intervention/management tool. Clearly new alternative drugs that are more affordable and with fewer side effects are desirable. After preliminary in vitro assays with plant growth regulators and inhibitors, here, we focus on biosynthetic inhibitors of gibberellin, a plant hormone with many important roles in plant growth, and show their inhibitory effect on the growth of both apicomplexa, Plasmodium falciparum and Toxoplasma gondii. Treatment of P. falciparum cultures with the gibberellin biosynthetic inhibitors resulted in marked morphological changes that can be reversed to a certain degree under hyperosmotic environment. These unique observations suggest that changes in the parasite membrane permeability may explain the pleiotropic effects observed within the intracellular parasites.

  14. Targeting of a Transporter to the Outer Apicoplast Membrane in the Human Malaria Parasite Plasmodium falciparum.

    Directory of Open Access Journals (Sweden)

    Liting Lim

    Full Text Available Apicoplasts are vestigial plastids in apicomplexan parasites like Plasmodium, the causative agent of malaria. Apicomplexan parasites are dependant on their apicoplasts for synthesis of various molecules that they are unable to scavenge in sufficient quantity from their host, which makes apicoplasts attractive drug targets. Proteins known as plastid phosphate translocators (pPTs are embedded in the outer apicoplast membrane and are responsible for the import of carbon, energy and reducing power to drive anabolic synthesis in the organelle. We investigated how a pPT is targeted into the outer apicoplast membrane of the human malaria parasite P. falciparum. We showed that a transmembrane domain is likely to act as a recessed signal anchor to direct the protein into the endomembrane system, and that a tyrosine in the cytosolic N-terminus of the protein is essential for targeting, but one or more, as yet unidentified, factors are also essential to direct the protein into the outer apicoplast membrane.

  15. 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...

  16. Perturbation and proinflammatory type activation of Vd1+ gamma delta T cells in African children with Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Hviid, L; Kurtzhals, J A; Adabayeri, V

    2001-01-01

    of Plasmodium falciparum malaria in Ghanaian children and they can constitute 30 to 50% of all T cells shortly after initiation of antimalarial chemotherapy. The bulk of the gamma delta T cells involved in this perturbation expressed V delta 1 and had a highly activated phenotype. Analysis of the T...... of the expanded V delta 1(+) T-cell population in this group of semi-immune P. falciparum malaria patients....

  17. Monitoring of Plasmodium infection in humans and potential vectors of malaria in a newly emerged focus in southern Iran.

    Science.gov (United States)

    Kalantari, Mohsen; Soltani, Zahra; Ebrahimi, Mostafa; Yousefi, Masoud; Amin, Masoumeh; Shafiei, Ayda; Azizi, Kourosh

    2017-02-01

    Despite control programs, which aim to eliminate malaria from Iran by 2025, transmission of malaria has not been removed from the country. This study aimed to monitor malaria from asymptomatic parasitaemia and clinical cases from about one year of active case surveillance and potential vectors of malaria in the newly emerged focus of Mamasani and Rostam, southern Iran during 2014-2015. Samples were collected and their DNAs were extracted for Polymerase Chain Reaction (PCR) assay using specific primers for detection of Plasmodium species. The Annual Parasite Incidence rate (API) was three cases per 1,000 population from 2,000 individuals in three villages. Parasites species were detected in 9 out of the 4,000 blood smear samples among which, 6 cases were indigenous and had no history of travels to endemic areas of malaria. Also, the prevalence rate of asymptomatic parasites was about 0.3%. Overall, 1073 Anopheles spp. were caught from 9 villages. Totally, 512 female samples were checked by PCR, which indicated that none of them was infected with Plasmodium. Despite new malaria local transmission in humans in Mamasani and Rostam districts, no infection with Plasmodium was observed in Anopheles species. Because of neighboring of the studied area to the re-emerged focus in Fars province (Kazerun) and important endemic foci of malaria in other southern provinces, such as Hormozgan and Kerman, monitoring of the vectors and reservoir hosts of Plasmodium species would be unavoidable. Application of molecular methods, such as PCR, can simplify access to the highest level of accuracy in malaria researches.

  18. 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....

  19. Advances in molecular genetic systems in malaria.

    Science.gov (United States)

    de Koning-Ward, Tania F; Gilson, Paul R; Crabb, Brendan S

    2015-06-01

    Robust tools for analysing gene function in Plasmodium parasites, which are the causative agents of malaria, are being developed at an accelerating rate. Two decades after genetic technologies for use in Plasmodium spp. were first described, a range of genetic tools are now available. These include conditional systems that can regulate gene expression at the genome, transcriptional or protein level, as well as more sophisticated tools for gene editing that use piggyBac transposases, integrases, zinc-finger nucleases or the CRISPR-Cas9 system. In this Review, we discuss the molecular genetic systems that are currently available for use in Plasmodium falciparum and Plasmodium berghei, and evaluate the advantages and limitations of these tools. We examine the insights that have been gained into the function of genes that are important during the blood stages of the parasites, which may help to guide the development and improvement of drug therapies and vaccines.

  20. [Diagnosis and treatment for three imported Plasmodium malariae malaria cases in Henan Province].

    Science.gov (United States)

    Deng, Yan; Zhou, Rui-Min; Zhang, Hong-Wei; Qian, Dan; Liu, Ying; Chen, Wei-Qi; Zhao, Xu-Dong

    2014-02-01

    Giemsa-stained blood film microscopy, CareStart rapid detection and PCR were used to detect the three cases who returned from Angola and Equatorial Guinea to Henan Province. Onset of malaria symptoms for two patients occurred 15 d and 27 d after their return from Angola, respectively. Two months after returning home, another case relapsed who had suffered from malaria in Equatorial Guinea. All three patients had the symptoms such as irregular fever, headache, chills and so on. Two cases had elevated total bilirubin and splenomegaly. The cases were confirmed as P. malariae infection by microscopic morphological examination. Amplified bands were produced by 18S rRNA nested PCR, which was the same with P. malariae in size, whereas the results of CareStart repaid detection test were all negative. They were cured by using artemisinin-based combination therapy (ACT).

  1. Plasmodium falciparum Protein Microarray Antibody Profiles Correlate With Protection From Symptomatic Malaria in Kenya.

    Science.gov (United States)

    Dent, Arlene E; Nakajima, Rie; Liang, Li; Baum, Elisabeth; Moormann, Ann M; Sumba, Peter Odada; Vulule, John; Babineau, Denise; Randall, Arlo; Davies, D Huw; Felgner, Philip L; Kazura, James W

    2015-11-01

    Immunoglobulin G antibodies (Abs) to Plasmodium falciparum antigens have been associated with naturally acquired immunity to symptomatic malaria. We probed protein microarrays covering 824 unique P. falciparum protein features with plasma from residents of a community in Kenya monitored for 12 weeks for (re)infection and symptomatic malaria after administration of antimalarial drugs. P. falciparum proteins recognized by Abs from 88 children (aged 1-14 years) and 86 adults (aged ≥ 18 years), measured at the beginning of the observation period, were ranked by Ab signal intensity. Abs from immune adults reacted with a total 163 of 824 P. falciparum proteins. Children gradually acquired Abs to the full repertoire of antigens recognized by adults. Abs to some antigens showed high seroconversion rates, reaching maximal levels early in childhood, whereas others did not reach adult levels until adolescence. No correlation between Ab signal intensity and time to (re)infection was observed. In contrast, Ab levels to 106 antigens were significantly higher in children who were protected from symptomatic malaria compared with those who were not. Abs to antigens predictive of protection included P. falciparum erythrocyte membrane protein 1, merozoite surface protein (MSP) 10, MSP2, liver-stage antigen 3, PF70, MSP7, and Plasmodium helical interspersed subtelomeric domain protein. Protein microarrays may be useful in the search for malaria antigens associated with protective immunity. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Plasmodium P-Type Cyclin CYC3 Modulates Endomitotic Growth during Oocyst Development in Mosquitoes.

    Science.gov (United States)

    Roques, Magali; Wall, Richard J; Douglass, Alexander P; Ramaprasad, Abhinay; Ferguson, David J P; Kaindama, Mbinda L; Brusini, Lorenzo; Joshi, Nimitray; Rchiad, Zineb; Brady, Declan; Guttery, David S; Wheatley, Sally P; Yamano, Hiroyuki; Holder, Anthony A; Pain, Arnab; Wickstead, Bill; Tewari, Rita

    2015-11-01

    Cell-cycle progression and cell division in eukaryotes are governed in part by the cyclin family and their regulation of cyclin-dependent kinases (CDKs). Cyclins are very well characterised in model systems such as yeast and human cells, but surprisingly little is known about their number and role in Plasmodium, the unicellular protozoan parasite that causes malaria. Malaria parasite cell division and proliferation differs from that of many eukaryotes. During its life cycle it undergoes two types of mitosis: endomitosis in asexual stages and an extremely rapid mitotic process during male gametogenesis. Both schizogony (producing merozoites) in host liver and red blood cells, and sporogony (producing sporozoites) in the mosquito vector, are endomitotic with repeated nuclear replication, without chromosome condensation, before cell division. The role of specific cyclins during Plasmodium cell proliferation was unknown. We show here that the Plasmodium genome contains only three cyclin genes, representing an unusual repertoire of cyclin classes. Expression and reverse genetic analyses of the single Plant (P)-type cyclin, CYC3, in the rodent malaria parasite, Plasmodium berghei, revealed a cytoplasmic and nuclear location of the GFP-tagged protein throughout the lifecycle. Deletion of cyc3 resulted in defects in size, number and growth of oocysts, with abnormalities in budding and sporozoite formation. Furthermore, global transcript analysis of the cyc3-deleted and wild type parasites at gametocyte and ookinete stages identified differentially expressed genes required for signalling, invasion and oocyst development. Collectively these data suggest that cyc3 modulates oocyst endomitotic development in Plasmodium berghei.

  3. Plasmodium P-Type Cyclin CYC3 Modulates Endomitotic Growth during Oocyst Development in Mosquitoes

    KAUST Repository

    Roques, Magali

    2015-11-13

    Cell-cycle progression and cell division in eukaryotes are governed in part by the cyclin family and their regulation of cyclin-dependent kinases (CDKs). Cyclins are very well characterised in model systems such as yeast and human cells, but surprisingly little is known about their number and role in Plasmodium, the unicellular protozoan parasite that causes malaria. Malaria parasite cell division and proliferation differs from that of many eukaryotes. During its life cycle it undergoes two types of mitosis: endomitosis in asexual stages and an extremely rapid mitotic process during male gametogenesis. Both schizogony (producing merozoites) in host liver and red blood cells, and sporogony (producing sporozoites) in the mosquito vector, are endomitotic with repeated nuclear replication, without chromosome condensation, before cell division. The role of specific cyclins during Plasmodium cell proliferation was unknown. We show here that the Plasmodium genome contains only three cyclin genes, representing an unusual repertoire of cyclin classes. Expression and reverse genetic analyses of the single Plant (P)-type cyclin, CYC3, in the rodent malaria parasite, Plasmodium berghei, revealed a cytoplasmic and nuclear location of the GFP-tagged protein throughout the lifecycle. Deletion of cyc3 resulted in defects in size, number and growth of oocysts, with abnormalities in budding and sporozoite formation. Furthermore, global transcript analysis of the cyc3-deleted and wild type parasites at gametocyte and ookinete stages identified differentially expressed genes required for signalling, invasion and oocyst development. Collectively these data suggest that cyc3 modulates oocyst endomitotic development in Plasmodium berghei.

  4. Plasmodium berghei ANKA: erythropoietin activates neural stem cells in an experimental cerebral malaria model

    DEFF Research Database (Denmark)

    Core, Andrew; Hempel, Casper; Kurtzhals, Jørgen A L

    2011-01-01

    investigated if EPO's neuroprotective effects include activation of endogenous neural stem cells (NSC). By using immunohistochemical markers of different NSC maturation stages, we show that EPO increased the number of nestin(+) cells in the dentate gyrus and in the sub-ventricular zone of the lateral...

  5. Tafenoquine and its potential in the treatment and relapse prevention of Plasmodium vivax malaria: the evidence to date.

    Science.gov (United States)

    Ebstie, Yehenew A; Abay, Solomon M; Tadesse, Wondmagegn T; Ejigu, Dawit A

    2016-01-01

    Despite declining global malaria incidence, the disease continues to be a threat to people living in endemic regions. In 2015, an estimated 214 million new malaria cases and 438,000 deaths due to malaria were recorded. Plasmodium vivax is the second most common cause of malaria next to Plasmodium falciparum. Vivax malaria is prevalent especially in Southeast Asia and the Horn of Africa, with enormous challenges in controlling the disease. Some of the challenges faced by vivax malaria-endemic countries include limited access to effective drugs treating liver stages of the parasite (schizonts and hypnozoites), emergence/spread of drug resistance, and misperception of vivax malaria as nonlethal. Primaquine, the only 8-aminoquinoline derivative approved by the US Food and Drug Administration, is intended to clear intrahepatic hypnozoites of P. vivax (radical cure). However, poor adherence to a prolonged treatment course, drug-induced hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency, and the emergence of resistance make it imperative to look for alternative drugs. Therefore, this review focuses on data accrued to date on tafenoquine and gives insight on the potential role of the drug in preventing relapse and radical cure of patients with vivax malaria.

  6. Characteristics of Travel-Related Severe Plasmodium vivax and Plasmodium falciparum Malaria in Individuals Hospitalized at a Tertiary Referral Center in Lima, Peru.

    Science.gov (United States)

    Llanos-Chea, Fiorella; Martínez, Dalila; Rosas, Angel; Samalvides, Frine; Vinetz, Joseph M; Llanos-Cuentas, Alejandro

    2015-12-01

    Severe Plasmodium falciparum malaria is uncommon in South America. Lima, Peru, while not endemic for malaria, is home to specialized centers for infectious diseases that admit and manage patients with severe malaria (SM), all of whom contracted infection during travel. This retrospective study describes severe travel-related malaria in individuals admitted to one tertiary care referral hospital in Lima, Peru; severity was classified based on criteria published by the World Health Organization in 2000. Data were abstracted from medical records of patients with SM admitted to Hospital Nacional Cayetano Heredia from 2006 to 2011. Of 33 SM cases with complete clinical data, the mean age was 39 years and the male/female ratio was 2.8. Most cases were contracted in known endemic regions within Peru: Amazonia (47%), the central jungle (18%), and the northern coast (12%); cases were also found in five (15%) travelers returning from Africa. Plasmodium vivax was most commonly identified (71%) among the severe infections, followed by P. falciparum (18%); mixed infections composed 11% of the group. Among the criteria of severity, jaundice was most common (58%), followed by severe thrombocytopenia (47%), hyperpyrexia (32%), and shock (15%). Plasmodium vivax mono-infection predominated as the etiology of SM in cases acquired in Peru.

  7. In vivo transmission blocking activities of artesunate on the avian malaria parasite Plasmodium gallinaceum.

    Science.gov (United States)

    Kumnuan, Rapeeporn; Pattaradilokrat, Sittiporn; Chumpolbanchorn, Kamlang; Pimnon, Suntorn; Narkpinit, Somphong; Harnyuttanakorn, Pongchai; Saiwichai, Tawee

    2013-11-08

    Infection and transmission of the avian malaria parasite Plasmodium gallinaceum in domestic chickens is associated with high economic burden and presents a major challenge to poultry industry in South East Asia. Development of drugs targeting both asexual blood stage parasites and sexual stages of the avian malarias will be beneficial for malaria treatment and eradication. However, current drugs recommended for treatment of the avian malaria parasites target specifically the asexual blood stage parasites, but have little or no impact to the gametocytes, the major target for development of transmission-blocking strategies. In the present work, we established a simple procedure to evaluate gametocytocidal and transmission blocking activities in a P. gallinaceum-avian model. The assays involved administration of seven consecutive daily doses of test compounds into P. gallinaceum-infected chickens with 10% parasitaemia and 1% gametocytaemia. Our studies indicated that intramuscular injection with seven daily low doses (the minimum effective dose of 10mg/kg) of artesunate blocked the gametocyte production and transmission to the mosquito vector Aedes aegypti. This assay can be further applicable for testing new compounds against P. gallinaceum and for other parasitic protozoa infecting birds.

  8. Genomics and Integrated Systems Biology in Plasmodium falciparum: A Path to Malaria Control and Eradication

    Science.gov (United States)

    Le Roch, Karine G.; Chung, Duk-Won D.; Ponts, Nadia

    2011-01-01

    The first draft of the human malaria parasite's genome was released in 2002. Since then, the malaria scientific community has witnessed a steady embrace of new and powerful functional genomic studies. Over the years, these approaches have slowly revolutionized malaria research and enabled the comprehensive, unbiased investigation of various aspects of the parasite's biology. These genome-wide analyses delivered a refined annotation of the parasite's genome, a better knowledge of its RNA, proteins, and metabolite derivatives, and fostered the discovery of new vaccine and drug targets. Despite the positive impacts of these genomic studies, most research and investment still focus on protein targets, drugs and vaccine candidates that were known before the publication of the parasite genome sequence. However, recent access to next-generation sequencing technologies, along with an increased number of genome-wide applications are expanding the impact of the parasite genome on biomedical research, contributing to a paradigm shift in research activities that may possibly lead to new optimized diagnosis and treatments. This review provides an update of Plasmodium falciparum genome sequences and an overview of the rapid development of genomics and system biology applications that have an immense potential of creating powerful tools for a successful malaria eradication campaign. PMID:21995286

  9. N-Terminal Plasmodium vivax Merozoite Surface Protein-1, a Potential Subunit for Malaria Vivax Vaccine

    Directory of Open Access Journals (Sweden)

    Fernanda G. Versiani

    2013-01-01

    Full Text Available The human malaria is widely distributed in the Middle East, Asia, the western Pacific, and Central and South America. Plasmodium vivax started to have the attention of many researchers since it is causing diseases to millions of people and several reports of severe malaria cases have been noticed in the last few years. The lack of in vitro cultures for P. vivax represents a major delay in developing a functional malaria vaccine. One of the major candidates to antimalarial vaccine is the merozoite surface protein-1 (MSP1, which is expressed abundantly on the merozoite surface and capable of activating the host protective immunity. Studies have shown that MSP-1 possesses highly immunogenic fragments, capable of generating immune response and protection in natural infection in endemic regions. This paper shows humoral immune response to different proteins of PvMSP1 and the statement of N-terminal to be added to the list of potential candidates for malaria vivax vaccine.

  10. The pathogenesis of Plasmodium falciparum malaria in humans: insights from splenic physiology

    Science.gov (United States)

    Safeukui, Innocent; Deplaine, Guillaume; Brousse, Valentine; Prendki, Virginie; Thellier, Marc; Turner, Gareth D.; Mercereau-Puijalon, Odile

    2011-01-01

    Clinical manifestations of Plasmodium falciparum infection are induced by the asexual stages of the parasite that develop inside red blood cells (RBCs). Because splenic microcirculatory beds filter out altered RBCs, the spleen can innately clear subpopulations of infected or uninfected RBC modified during falciparum malaria. The spleen appears more protective against severe manifestations of malaria in naïve than in immune subjects. The spleen-specific pitting function accounts for a large fraction of parasite clearance in artemisinin-treated patients. RBC loss contributes to malarial anemia, a clinical form associated with subacute progression, frequent splenomegaly, and relatively low parasitemia. Stringent splenic clearance of ring-infected RBCs and uninfected, but parasite-altered, RBCs, may altogether exacerbate anemia and reduce the risks of severe complications associated with high parasite loads, such as cerebral malaria. The age of the patient directly influences the risk of severe manifestations. We hypothesize that coevolution resulting in increased splenic clearance of P. falciparum–altered RBCs in children favors the survival of the host and, ultimately, sustained parasite transmission. This analysis of the RBC–spleen dynamic interactions during P falciparum infection reflects both data and hypotheses, and provides a framework on which a more complete immunologic understanding of malaria pathogenesis may be elaborated. PMID:20852127

  11. 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.

  12. Standardization of the antibody-dependent respiratory burst assay with human neutrophils and Plasmodium falciparum malaria.

    Science.gov (United States)

    Llewellyn, David; Miura, Kazutoyo; Fay, Michael P; Williams, Andrew R; Murungi, Linda M; Shi, Jianguo; Hodgson, Susanne H; Douglas, Alexander D; Osier, Faith H; Fairhurst, Rick M; Diakite, Mahamadou; Pleass, Richard J; Long, Carole A; Draper, Simon J

    2015-09-16

    The assessment of naturally-acquired and vaccine-induced immunity to blood-stage Plasmodium falciparum malaria is of long-standing interest. However, the field has suffered from a paucity of in vitro assays that reproducibly measure the anti-parasitic activity induced by antibodies in conjunction with immune cells. Here we optimize the antibody-dependent respiratory burst (ADRB) assay, which assesses the ability of antibodies to activate the release of reactive oxygen species from human neutrophils in response to P. falciparum blood-stage parasites. We focus particularly on assay parameters affecting serum preparation and concentration, and importantly assess reproducibility. Our standardized protocol involves testing each serum sample in singlicate with three independent neutrophil donors, and indexing responses against a standard positive control of pooled hyper-immune Kenyan sera. The protocol can be used to quickly screen large cohorts of samples from individuals enrolled in immuno-epidemiological studies or clinical vaccine trials, and requires only 6 μL of serum per sample. Using a cohort of 86 samples, we show that malaria-exposed individuals induce higher ADRB activity than malaria-naïve individuals. The development of the ADRB assay complements the use of cell-independent assays in blood-stage malaria, such as the assay of growth inhibitory activity, and provides an important standardized cell-based assay in the field.

  13. Three cases of ARDS: An emerging complication of Plasmodium vivax malaria

    Directory of Open Access Journals (Sweden)

    Sarkar Supriya

    2010-01-01

    Full Text Available Plasmodium (P. vivax malaria is rarely associated with severe complications like acute respiratory distress syndrome (ARDS. We report three cases of ARDS, which occurred as a complication of vivax malaria, from the city of Kolkata. A middle aged man who developed ARDS along with hepatic and renal dysfunction on the day 7 after completion of antimalarial treatment; a 36-year-old man who developed ARDS on the day 5 after completion of antimalarial treatment and a 15-year-old boy who developed ARDS on day 2, before starting anti-malarial drug. In all cases, vivax malaria was diagnosed by peripheral blood film (PBF examination. Associated falciparum infection was excluded by repeated PBF examination, and by negative P. falciparum malaria antigen tests. In all cases, ARDS was diagnosed by the presence of hypoxia with PaO 2 / FiO 2 ratio < 200 and bilateral pulmonary infiltration, and by excluding cardiac disease by echocardiography. All cases typically had dramatic onset of ARDS, and required immediate (within hour of onset of dyspnea institution of mechanical ventilation with high positive end expiratory pressure. All three cases recovered completely, and early ventilator support was life-saving.

  14. Insights into the pyrimidine biosynthetic pathway of human malaria parasite Plasmodium falciparum as chemotherapeutic target.

    Science.gov (United States)

    Krungkrai, Sudaratana R; Krungkrai, Jerapan

    2016-06-01

    Malaria is a major cause of morbidity and mortality in humans. Artemisinins remain as the first-line treatment for Plasmodium falciparum (P. falciparum) malaria although drug resistance has already emerged and spread in Southeast Asia. Thus, to fight this disease, there is an urgent need to develop new antimalarial drugs for malaria chemotherapy. Unlike human host cells, P. falciparum cannot salvage preformed pyrimidine bases or nucleosides from the extracellular environment and relies solely on nucleotides synthesized through the de novo biosynthetic pathway. This review presents significant progress on understanding the de novo pyrimidine pathway and the functional enzymes in the human parasite P. falciparum. Current knowledge in genomics and metabolomics are described, particularly focusing on the parasite purine and pyrimidine nucleotide metabolism. These include gene annotation, characterization and molecular mechanism of the enzymes that are different from the human host pathway. Recent elucidation of the three-dimensional crystal structures and the catalytic reactions of three enzymes: dihydroorotate dehydrogenase, orotate phosphoribosyltransferase, and orotidine 5'-monophosphate decarboxylase, as well as their inhibitors are reviewed in the context of their therapeutic potential against malaria.

  15. 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.

  16. Spleen volume and clinical disease manifestations of severe Plasmodium falciparum malaria in African children.

    Science.gov (United States)

    Kotlyar, Simon; Nteziyaremye, Julius; Olupot-Olupot, Peter; Akech, Samuel O; Moore, Christopher L; Maitland, Kathryn

    2014-05-01

    Plasmodium falciparum malaria is common in African children. Severe disease manifestations include severe malarial anemia (SMA) and cerebral malaria (CM). In vitro studies suggest that splenic sequestration is associated with SMA and protective against CM. We sought to characterize the relationship between ultrasonographically derived spleen volume (SV), clinical manifestations and outcome. We conducted a prospective observational study of severe malaria and SV in children aged 3 months to 12 years in Eastern Uganda. An SV normogram was generated from 186 healthy controls and adjusted for total body surface area (TBSA). Children with severe P. falciparum malaria were classified according to disease phenotype, and SV z-scores were compared for cases and controls to assess the degree of spleen enlargement. One hundred and four children with severe malaria, median age 19.2 months, were enrolled; 54 were classified as having SMA and 15 with CM. Mortality was 27% in the CM group vs 1.9% in the SMA group. TBSA-adjusted SV z-scores were lower in children with CM compared to SMA (1.98 [95% CI 1.38-2.57] vs 2.73 [95% CI 2.41-3.04]; p=0.028). Mean SV z-scores were lower in children who died (1.20 [95% CI 0.14-2.25]) compared to survivors (2.58 [95% CI 2.35-2.81]); p=0.004. SV is lower in CM compared to SMA. Severe malaria with no increase in SV z-score may be associated with mortality.

  17. Haemoglobin C and S role in acquired immunity against Plasmodium falciparum malaria.

    Directory of Open Access Journals (Sweden)

    Federica Verra

    Full Text Available A recently proposed mechanism of protection for haemoglobin C (HbC; beta6Glu-->Lys links an abnormal display of PfEMP1, an antigen involved in malaria pathogenesis, on the surface of HbC infected erythrocytes together with the observation of reduced cytoadhesion of parasitized erythrocytes and impaired rosetting in vitro. We investigated the impact of this hypothesis on the development of acquired immunity against Plasmodium falciparum variant surface antigens (VSA encoding PfEMP1 in HbC in comparison with HbA and HbS carriers of Burkina Faso. We measured: i total IgG against a single VSA, A4U, and against a panel of VSA from severe malaria cases in human sera from urban and rural areas of Burkina Faso of different haemoglobin genotypes (CC, AC, AS, SC, SS; ii total IgG against recombinant proteins of P. falciparum asexual sporozoite, blood stage antigens, and parasite schizont extract; iii total IgG against tetanus toxoid. Results showed that the reported abnormal cell-surface display of PfEMP1 on HbC infected erythrocytes observed in vitro is not associated to lower anti- PfEMP1 response in vivo. Higher immune response against the VSA panel and malaria antigens were observed in all adaptive genotypes containing at least one allelic variant HbC or HbS in the low transmission urban area whereas no differences were detected in the high transmission rural area. In both contexts the response against tetanus toxoid was not influenced by the beta-globin genotype. These findings suggest that both HbC and HbS affect the early development of naturally acquired immunity against malaria. The enhanced immune reactivity in both HbC and HbS carriers supports the hypothesis that the protection against malaria of these adaptive genotypes might be at least partially mediated by acquired immunity against malaria.

  18. Optimized Pan-species and Speciation Duplex Real-time PCR Assays for Plasmodium Parasites Detection in Malaria Vectors

    Science.gov (United States)

    Sandeu, Maurice Marcel; Moussiliou, Azizath; Moiroux, Nicolas; Padonou, Gilles G.; Massougbodji, Achille; Corbel, Vincent; Tuikue Ndam, Nicaise

    2012-01-01

    Background An accurate method for detecting malaria parasites in the mosquito’s vector remains an essential component in the vector control. The Enzyme linked immunosorbent assay specific for circumsporozoite protein (ELISA-CSP) is the gold standard method for the detection of malaria parasites in the vector even if it presents some limitations. Here, we optimized multiplex real-time PCR assays to accurately detect minor populations in mixed infection with multiple Plasmodium species in the African malaria vectors Anopheles gambiae and Anopheles funestus. Methods Complementary TaqMan-based real-time PCR assays that detect Plasmodium species using specific primers and probes were first evaluated on artificial mixtures of different targets inserted in plasmid constructs. The assays were further validated in comparison with the ELISA-CSP on 200 field caught Anopheles gambiae and Anopheles funestus mosquitoes collected in two localities in southern Benin. Results The validation of the duplex real-time PCR assays on the plasmid mixtures demonstrated robust specificity and sensitivity for detecting distinct targets. Using a panel of mosquito specimen, the real-time PCR showed a relatively high sensitivity (88.6%) and specificity (98%), compared to ELISA-CSP as the referent standard. The agreement between both methods was “excellent” (κ = 0.8, PPlasmodium DNA between the two Anopheles species analyzed showed no significant difference (P = 0, 2). All infected mosquito samples contained Plasmodium falciparum DNA and mixed infections with P. malariae and/or P. ovale were observed in 18.6% and 13.6% of An. gambiae and An. funestus respectively. Plasmodium vivax was found in none of the mosquito samples analyzed. Conclusion This study presents an optimized method for detecting the four Plasmodium species in the African malaria vectors. The study highlights substantial discordance with traditional ELISA-CSP pointing out the utility of employing an accurate

  19. Epidemiology of Plasmodium knowlesi malaria in north-east Sabah, Malaysia: family clusters and wide age distribution

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    Barber Bridget E

    2012-12-01

    Full Text Available Abstract Background The simian parasite Plasmodium knowlesi is a common cause of human malaria in Malaysian Borneo, with a particularly high incidence in Kudat, Sabah. Little is known however about the epidemiology in this substantially deforested region. Methods Malaria microscopy records at Kudat District Hospital were retrospectively reviewed from January 2009-November 2011. Demographics, and PCR results if available, were recorded for each positive result. Medical records were reviewed for patients suspected of representing family clusters, and families contacted for further information. Rainfall data were obtained from the Malaysian Meteorological Department. Results “Plasmodium malariae” mixed or mono-infection was diagnosed by microscopy in 517/653 (79% patients. Of these, PCR was performed in 445 (86% and was positive for P. knowlesi mono-infection in 339 (76%. Patients with knowlesi malaria demonstrated a wide age distribution (median 33, IQR 20–50, range 0.7-89 years with P. knowlesi predominating in all age groups except those Plasmodium falciparum and Plasmodium vivax. Two contemporaneous family clusters were identified: a father with two children (aged 10–11 years; and three brothers (aged one-11 years, all with PCR-confirmed knowlesi malaria. Cases of P. knowlesi demonstrated significant seasonal variation, and correlated with rainfall in the preceding three to five months. Conclusions Plasmodium knowlesi is the most common cause of malaria admissions to Kudat District Hospital. The wide age distribution and presence of family clusters suggest that transmission may be occurring close to or inside people’s homes, in contrast to previous reports from densely forested areas of Sarawak. These findings have significant implications for malaria control. Prospective studies of risk factors, vectors and transmission dynamics of P. knowlesi in Sabah, including potential for human-to-human transmission, are needed.

  20. Oxidative stress and modification of renal vascular permeability are associated with acute kidney injury during P. berghei ANKA infection.

    Science.gov (United States)

    Elias, Rosa Maria; Correa-Costa, Matheus; Barreto, Claudiene Rodrigues; Silva, Reinaldo Correia; Hayashida, Caroline Y; Castoldi, Angela; Gonçalves, Giselle Martins; Braga, Tarcio Teodoro; Barboza, Renato; Rios, Francisco José; Keller, Alexandre Castro; Cenedeze, Marcos Antonio; Hyane, Meire Ioshie; D'Império-Lima, Maria Regina; Figueiredo-Neto, Antônio Martins; Reis, Marlene Antônia; Marinho, Cláudio Romero Farias; Pacheco-Silva, Alvaro; Câmara, Niels Olsen Saraiva

    2012-01-01

    Malaria associated-acute kidney injury (AKI) is associated with 45% of mortality in adult patients hospitalized with severe form of the disease. However, the causes that lead to a framework of malaria-associated AKI are still poorly characterized. Some clinical studies speculate that oxidative stress products, a characteristic of Plasmodium infection, as well as proinflammatory response induced by the parasite are involved in its pathophysiology. Therefore, we aimed to investigate the development of malaria-associated AKI during infection by P. berghei ANKA, with special attention to the role played by the inflammatory response and the involvement of oxidative stress. For that, we took advantage of an experimental model of severe malaria that showed significant changes in the renal pathophysiology to investigate the role of malaria infection in the renal microvascular permeability and tissue injury. Therefore, BALB/c mice were infected with P. berghei ANKA. To assess renal function, creatinine, blood urea nitrogen, and ratio of proteinuria and creatininuria were evaluated. The products of oxidative stress, as well as cytokine profile were quantified in plasma and renal tissue. The change of renal microvascular permeability, tissue hypoxia and cellular apoptosis were also evaluated. Parasite infection resulted in renal dysfunction. Furthermore, we observed increased expression of adhesion molecule, proinflammatory cytokines and products of oxidative stress, associated with a decrease mRNA expression of HO-1 in kidney tissue of infected mice. The measurement of lipoprotein oxidizability also showed a significant increase in plasma of infected animals. Together, our findings support the idea that products of oxidative stress, as well as the immune response against the parasite are crucial to changes in kidney architecture and microvascular endothelial permeability of BALB/c mice infected with P. berghei ANKA.

  1. Oxidative Stress and Modification of Renal Vascular Permeability Are Associated with Acute Kidney Injury during P. berghei ANKA Infection

    Science.gov (United States)

    Elias, Rosa Maria; Correa-Costa, Matheus; Barreto, Claudiene Rodrigues; Silva, Reinaldo Correia; Hayashida, Caroline Y.; Castoldi, Ângela; Gonçalves, Giselle Martins; Braga, Tarcio Teodoro; Barboza, Renato; Rios, Francisco José; Keller, Alexandre Castro; Cenedeze, Marcos Antonio; Hyane, Meire Ioshie; D'Império-Lima, Maria Regina; Figueiredo-Neto, Antônio Martins; Reis, Marlene Antônia; Marinho, Cláudio Romero Farias; Pacheco-Silva, Alvaro; Câmara, Niels Olsen Saraiva

    2012-01-01

    Malaria associated-acute kidney injury (AKI) is associated with 45% of mortality in adult patients hospitalized with severe form of the disease. However, the causes that lead to a framework of malaria-associated AKI are still poorly characterized. Some clinical studies speculate that oxidative stress products, a characteristic of Plasmodium infection, as well as proinflammatory response induced by the parasite are involved in its pathophysiology. Therefore, we aimed to investigate the development of malaria-associated AKI during infection by P. berghei ANKA, with special attention to the role played by the inflammatory response and the involvement of oxidative stress. For that, we took advantage of an experimental model of severe malaria that showed significant changes in the renal pathophysiology to investigate the role of malaria infection in the renal microvascular permeability and tissue injury. Therefore, BALB/c mice were infected with P. berghei ANKA. To assess renal function, creatinine, blood urea nitrogen, and ratio of proteinuria and creatininuria were evaluated. The products of oxidative stress, as well as cytokine profile were quantified in plasma and renal tissue. The change of renal microvascular permeability, tissue hypoxia and cellular apoptosis were also evaluated. Parasite infection resulted in renal dysfunction. Furthermore, we observed increased expression of adhesion molecule, proinflammatory cytokines and products of oxidative stress, associated with a decrease mRNA expression of HO-1 in kidney tissue of infected mice. The measurement of lipoprotein oxidizability also showed a significant increase in plasma of infected animals. Together, our findings support the idea that products of oxidative stress, as well as the immune response against the parasite are crucial to changes in kidney architecture and microvascular endothelial permeability of BALB/c mice infected with P. berghei ANKA. PMID:22952850

  2. Using infective mosquitoes to challenge monkeys with Plasmodium knowlesi in malaria vaccine studies

    Science.gov (United States)

    2014-01-01

    Background When rhesus monkeys (Macaca mulatta) are used to test malaria vaccines, animals are often challenged by the intravenous injection of sporozoites. However, natural exposure to malaria comes via mosquito bite, and antibodies can neutralize sporozoites as they traverse the skin. Thus, intravenous injection may not fairly assess humoral immunity from anti-sporozoite malaria vaccines. To better assess malaria vaccines in rhesus, a method to challenge large numbers of monkeys by mosquito bite was developed. Methods Several species and strains of mosquitoes were tested for their ability to produce Plasmodium knowlesi sporozoites. Donor monkey parasitaemia effects on oocyst and sporozoite numbers and mosquito mortality were documented. Methylparaben added to mosquito feed was tested to improve mosquito survival. To determine the number of bites needed to infect a monkey, animals were exposed to various numbers of P. knowlesi-infected mosquitoes. Finally, P. knowlesi-infected mosquitoes wer