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Sample records for malaria parasites infecting

  1. Implications of malaria and intestinal parasitic co-infections among ...

    The prevalence of malaria and gastrointestinal parasitic infections in out-patients of Federal Medical Center (FMC) Owerri Specialist Hospital, was studied between the months of January and June 2004. A total of 1,200 patients made up of preschool children (400), school children (400) and adults (400) were enlisted for the ...

  2. The fitness of drug-resistant malaria parasites in a rodent model: multiplicity of infection

    Huijben, Silvie; Sim, Derek G.; Nelson, William, A.; Read, Andrew F.

    2011-01-01

    Malaria infections normally consist of more than one clonally-replicating lineage. Within-host interactions between sensitive and resistant parasites can have profound effects on the evolution of drug resistance. Here, using the Plasmodium chabaudi mouse malaria model, we ask whether the costs and benefits of resistance are affected by the number of co-infecting strains competing with a resistant clone. We found strong competitive suppression of resistant parasites in untreated infections and...

  3. Wild Anopheles funestus mosquito genotypes are permissive for infection with the rodent malaria parasite, Plasmodium berghei.

    Jiannong Xu

    Full Text Available Malaria parasites undergo complex developmental transitions within the mosquito vector. A commonly used laboratory model for studies of mosquito-malaria interaction is the rodent parasite, P. berghei. Anopheles funestus is a major malaria vector in sub-Saharan Africa but has received less attention than the sympatric species, Anopheles gambiae. The imminent completion of the A. funestus genome sequence will provide currently lacking molecular tools to describe malaria parasite interactions in this mosquito, but previous reports suggested that A. funestus is not permissive for P. berghei development.An A. funestus population was generated in the laboratory by capturing female wild mosquitoes in Mali, allowing them to oviposit, and rearing the eggs to adults. These F1 progeny of wild mosquitoes were allowed to feed on mice infected with a fluorescent P. berghei strain. Fluorescence microscopy was used to track parasite development inside the mosquito, salivary gland sporozoites were tested for infectivity to mice, and parasite development in A. funestus was compared to A. gambiae.P. berghei oocysts were detectable on A. funestus midguts by 7 days post-infection. By 18-20 days post-infection, sporozoites had invaded the median and distal lateral lobes of the salivary glands, and hemocoel sporozoites were observed in the hemolymph. Mosquitoes were capable of infecting mice via bite, demonstrating that A. funestus supports the complete life cycle of P. berghei. In a random sample of wild mosquito genotypes, A. funestus prevalence of infection and the characteristics of parasite development were similar to that observed in A. gambiae-P. berghei infections.The data presented in this study establish an experimental laboratory model for Plasmodium infection of A. funestus, an important vector of human malaria. Studying A. funestus-Plasmodium interactions is now feasible in a laboratory setting. This information lays the groundwork for exploitation of the

  4. Natural infection of Plasmodium brasilianum in humans: Man and monkey share quartan malaria parasites in the Venezuelan Amazon

    Albert Lalremruata

    2015-09-01

    Interpretation: 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.

  5. MHC-I affects infection intensity but not infection status with a frequent avian malaria parasite in blue tits.

    Helena Westerdahl

    Full Text Available Host resistance against parasites depends on three aspects: the ability to prevent, control and clear infections. In vertebrates the immune system consists of innate and adaptive immunity. Innate immunity is particularly important for preventing infection and eradicating established infections at an early stage while adaptive immunity is slow, but powerful, and essential for controlling infection intensities and eventually clearing infections. Major Histocompatibility Complex (MHC molecules are central in adaptive immunity, and studies on parasite resistance and MHC in wild animals have found effects on both infection intensity (parasite load and infection status (infected or not. It seems MHC can affect both the ability to control infection intensities and the ability to clear infections. However, these two aspects have rarely been considered simultaneously, and their relative importance in natural populations is therefore unclear. Here we investigate if MHC class I genotype affects infection intensity and infection status with a frequent avian malaria infection Haemoproteus majoris in a natural population of blue tits Cyanistes caeruleus. We found a significant negative association between a single MHC allele and infection intensity but no association with infection status. Blue tits that carry a specific MHC allele seem able to suppress H. majoris infection intensity, while we have no evidence that this allele also has an effect on clearance of the H. majoris infection, a result that is in contrast with some previous studies of MHC and avian malaria. A likely explanation could be that the clearance rate of avian malaria parasites differs between avian malaria lineages and/or between avian hosts.

  6. MHC-I affects infection intensity but not infection status with a frequent avian malaria parasite in blue tits.

    Westerdahl, Helena; Stjernman, Martin; Råberg, Lars; Lannefors, Mimi; Nilsson, Jan-Åke

    2013-01-01

    Host resistance against parasites depends on three aspects: the ability to prevent, control and clear infections. In vertebrates the immune system consists of innate and adaptive immunity. Innate immunity is particularly important for preventing infection and eradicating established infections at an early stage while adaptive immunity is slow, but powerful, and essential for controlling infection intensities and eventually clearing infections. Major Histocompatibility Complex (MHC) molecules are central in adaptive immunity, and studies on parasite resistance and MHC in wild animals have found effects on both infection intensity (parasite load) and infection status (infected or not). It seems MHC can affect both the ability to control infection intensities and the ability to clear infections. However, these two aspects have rarely been considered simultaneously, and their relative importance in natural populations is therefore unclear. Here we investigate if MHC class I genotype affects infection intensity and infection status with a frequent avian malaria infection Haemoproteus majoris in a natural population of blue tits Cyanistes caeruleus. We found a significant negative association between a single MHC allele and infection intensity but no association with infection status. Blue tits that carry a specific MHC allele seem able to suppress H. majoris infection intensity, while we have no evidence that this allele also has an effect on clearance of the H. majoris infection, a result that is in contrast with some previous studies of MHC and avian malaria. A likely explanation could be that the clearance rate of avian malaria parasites differs between avian malaria lineages and/or between avian hosts.

  7. Hamatological parameters and malaria parasite infection among pregnant women in Northwest Nigeria

    Anigo Kola Matthew

    2013-02-01

    Full Text Available Objective: To evaluate some hematological and anthropometric parameters, malaria infection at different trimesters in pregnancy. Methods: Fifty pregnant women (6 in first trimester, 28 in second trimester and 16 in third trimester between ages of 15-40 years with ten age-matched non-pregnant women used as control were enrolled in the study. Consent were obtained from the subjects after which semi-structured questionnaires were administered to obtain data on demographic and socio-economic variables, reproductive and medical history. Anthropometric variables, and hematology were carried out using standard procedures. Results: Anthropometric characteristics showed no significant difference in weight, height and BMI when compared with non-pregnant control. Hematological values indicated higher values for non-pregnant women but not statistically significant. Prevalence of malaria infection in pregnant women showed that 40% of pregnant women examined were infected compared to 30% non-pregnant with those with first pregnancy (primagravid recording the highest infection (47.62% with pregnant women within age 15-18 years least infected (16.7%. Pregnant women in the third trimester had the highest (50% malaria infection and there was increase in prevalence with increase education status and those with first pregnancy (primagravid recorded the highest infection (47.62%. Treatment used when infected showed 36.8% and 42.9% used malaria drug and both drug/herbs respectively. Conclusions: Higher prevalence rate of malaria infection in pregnant women with the highest prevalence recorded in those with first conception (primigravidae. There is a need for continuous monitoring of hematological parameters and malaria parasite infection for better outcome of pregnancy.

  8. Natural infection of Plasmodium brasilianum in humans: Man and monkey share quartan malaria parasites in the Venezuelan Amazon.

    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.

  9. The Strategy to Survive Primary Malaria Infection: An Experimental Study on Behavioural Changes in Parasitized Birds.

    Andrey Mukhin

    Full Text Available Avian malaria parasites (Haemosporida, Plasmodium are of cosmopolitan distribution, and they have a significant impact on vertebrate host fitness. Experimental studies show that high parasitemia often develops during primary malaria infections. However, field studies only occasionally reveal high parasitemia in free-living birds sampled using the traditional methods of mist-netting or trapping, and light chronic infections predominate. The reason for this discrepancy between field observation and experimental data remains insufficiently understood. Since mist-netting is a passive capture method, two main parameters determine its success in sampling infected birds in wildlife, i. e. the presence of parasitized birds at a study site and their mobility. In other words, the trapping probability depends on the survival rate of birds and their locomotor activity during infection. Here we test (1 the mortality rate of wild birds infected with Plasmodium relictum (the lineage pSGS1, (2 the changes in their behaviour during presence of an aerial predator, and (3 the changes in their locomotor activity at the stage of high primary parasitemia.We show that some behavioural features which might affect a bird's survival during a predator attack (time of reaction, speed of flush flight and take off angle did not change significantly during primary infection. However, the locomotor activity of infected birds was almost halved compared to control (non-infected birds during the peak of parasitemia. We report (1 the markedly reduced mobility and (2 the 20% mortality rate caused by P. relictum and conclude that these factors are responsible for the underrepresentation of birds in mist nets and traps during the stage of high primary parasitemia in wildlife. This study indicates that the widespread parasite, P. relictum (pSGS1 influences the behaviour of birds during primary parasitemia. Experimental studies combined with field observations are needed to better

  10. The Strategy to Survive Primary Malaria Infection: An Experimental Study on Behavioural Changes in Parasitized Birds

    Mukhin, Andrey; Palinauskas, Vaidas; Platonova, Elena; Kobylkov, Dmitry; Vakoliuk, Irina; Valkiūnas, Gediminas

    2016-01-01

    Avian malaria parasites (Haemosporida, Plasmodium) are of cosmopolitan distribution, and they have a significant impact on vertebrate host fitness. Experimental studies show that high parasitemia often develops during primary malaria infections. However, field studies only occasionally reveal high parasitemia in free-living birds sampled using the traditional methods of mist-netting or trapping, and light chronic infections predominate. The reason for this discrepancy between field observation and experimental data remains insufficiently understood. Since mist-netting is a passive capture method, two main parameters determine its success in sampling infected birds in wildlife, i. e. the presence of parasitized birds at a study site and their mobility. In other words, the trapping probability depends on the survival rate of birds and their locomotor activity during infection. Here we test (1) the mortality rate of wild birds infected with Plasmodium relictum (the lineage pSGS1), (2) the changes in their behaviour during presence of an aerial predator, and (3) the changes in their locomotor activity at the stage of high primary parasitemia.We show that some behavioural features which might affect a bird's survival during a predator attack (time of reaction, speed of flush flight and take off angle) did not change significantly during primary infection. However, the locomotor activity of infected birds was almost halved compared to control (non-infected) birds during the peak of parasitemia. We report (1) the markedly reduced mobility and (2) the 20% mortality rate caused by P. relictum and conclude that these factors are responsible for the underrepresentation of birds in mist nets and traps during the stage of high primary parasitemia in wildlife. This study indicates that the widespread parasite, P. relictum (pSGS1) influences the behaviour of birds during primary parasitemia. Experimental studies combined with field observations are needed to better understand the

  11. Leukocyte profiles for western fence lizards, Sceloporus occidentalis, naturally infected by the malaria parasite Plasmodium mexicanum.

    Motz, Victoria L; Lewis, William D; Vardo-Zalik, Anne M

    2014-10-01

    Plasmodium mexicanum is a malaria parasite that naturally infects the western fence lizard, Sceloporus occidentalis , in northern California. We set out to determine whether lizards naturally infected with this malaria parasite have different leukocyte profiles, indicating an immune response to infection. We used 29 naturally infected western fence lizards paired with uninfected lizards based on sex, snout-to-vent length, tail status, and the presence-absence of ectoparasites such as ticks and mites, as well as the presence-absence of another hemoparasite, Schellackia occidentalis. Complete white blood cell (WBC) counts were conducted on blood smears stained with Giemsa, and the proportion of granulocytes per microliter of blood was estimated using the Avian Leukopet method. The abundance of each WBC class (lymphocytes, monocytes, heterophils, eosinophils, and basophils) in infected and uninfected lizards was compared to determine whether leukocyte densities varied with infection status. We found that the numbers of WBCs and lymphocytes per microliter of blood significantly differed (P lizard's immune response to increase the levels of circulating WBCs, but what effect this has on the biology of the parasite remains unclear.

  12. Neglected Parasitic Infections: Toxocariasis

    This podcast is an overview of the Clinician Outreach and Communication Activity (COCA) Call: Neglected Parasitic Infections in the United States. Neglected Parasitic Infections are a group of diseases that afflict vulnerable populations and are often not well studied or diagnosed. A subject matter expert from CDC's Division of Parasitic Diseases and Malaria describes the epidemiology, diagnosis, and treatment of toxocariasis.

  13. Antitumor effect of malaria parasite infection in a murine Lewis lung cancer model through induction of innate and adaptive immunity.

    Chen, Lili; He, Zhengxiang; Qin, Li; Li, Qinyan; Shi, Xibao; Zhao, Siting; Chen, Ling; Zhong, Nanshan; Chen, Xiaoping

    2011-01-01

    Lung cancer is the most common malignancy in humans and its high fatality means that no effective treatment is available. Developing new therapeutic strategies for lung cancer is urgently needed. Malaria has been reported to stimulate host immune responses, which are believed to be efficacious for combating some clinical cancers. This study is aimed to provide evidence that malaria parasite infection is therapeutic for lung cancer. Antitumor effect of malaria infection was examined in both subcutaneously and intravenously implanted murine Lewis lung cancer (LLC) model. The results showed that malaria infection inhibited LLC growth and metastasis and prolonged the survival of tumor-bearing mice. Histological analysis of tumors from mice infected with malaria revealed that angiogenesis was inhibited, which correlated with increased terminal deoxynucleotidyl transferase-mediated (TUNEL) staining and decreased Ki-67 expression in tumors. Through natural killer (NK) cell cytotoxicity activity, cytokine assays, enzyme-linked immunospot assay, lymphocyte proliferation, and flow cytometry, we demonstrated that malaria infection provided anti-tumor effects by inducing both a potent anti-tumor innate immune response, including the secretion of IFN-γ and TNF-α and the activation of NK cells as well as adaptive anti-tumor immunity with increasing tumor-specific T-cell proliferation and cytolytic activity of CD8(+) T cells. Notably, tumor-bearing mice infected with the parasite developed long-lasting and effective tumor-specific immunity. Consequently, we found that malaria parasite infection could enhance the immune response of lung cancer DNA vaccine pcDNA3.1-hMUC1 and the combination produced a synergistic antitumor effect. Malaria infection significantly suppresses LLC growth via induction of innate and adaptive antitumor responses in a mouse model. These data suggest that the malaria parasite may provide a novel strategy or therapeutic vaccine vector for anti-lung cancer

  14. Antitumor effect of malaria parasite infection in a murine Lewis lung cancer model through induction of innate and adaptive immunity.

    Lili Chen

    Full Text Available BACKGROUND: Lung cancer is the most common malignancy in humans and its high fatality means that no effective treatment is available. Developing new therapeutic strategies for lung cancer is urgently needed. Malaria has been reported to stimulate host immune responses, which are believed to be efficacious for combating some clinical cancers. This study is aimed to provide evidence that malaria parasite infection is therapeutic for lung cancer. METHODOLOGY/PRINCIPAL FINDINGS: Antitumor effect of malaria infection was examined in both subcutaneously and intravenously implanted murine Lewis lung cancer (LLC model. The results showed that malaria infection inhibited LLC growth and metastasis and prolonged the survival of tumor-bearing mice. Histological analysis of tumors from mice infected with malaria revealed that angiogenesis was inhibited, which correlated with increased terminal deoxynucleotidyl transferase-mediated (TUNEL staining and decreased Ki-67 expression in tumors. Through natural killer (NK cell cytotoxicity activity, cytokine assays, enzyme-linked immunospot assay, lymphocyte proliferation, and flow cytometry, we demonstrated that malaria infection provided anti-tumor effects by inducing both a potent anti-tumor innate immune response, including the secretion of IFN-γ and TNF-α and the activation of NK cells as well as adaptive anti-tumor immunity with increasing tumor-specific T-cell proliferation and cytolytic activity of CD8(+ T cells. Notably, tumor-bearing mice infected with the parasite developed long-lasting and effective tumor-specific immunity. Consequently, we found that malaria parasite infection could enhance the immune response of lung cancer DNA vaccine pcDNA3.1-hMUC1 and the combination produced a synergistic antitumor effect. CONCLUSIONS/SIGNIFICANCE: Malaria infection significantly suppresses LLC growth via induction of innate and adaptive antitumor responses in a mouse model. These data suggest that the malaria

  15. Cytoplasmic free Ca2+ is essential for multiple steps in malaria parasite egress from infected erythrocytes

    Glushakova Svetlana

    2013-01-01

    Full Text Available Abstract Background Egress of Plasmodium falciparum, from erythrocytes at the end of its asexual cycle and subsequent parasite invasion into new host cells, is responsible for parasite dissemination in the human body. The egress pathway is emerging as a coordinated multistep programme that extends in time for tens of minutes, ending with rapid parasite extrusion from erythrocytes. While the Ca2+ regulation of the invasion of P. falciparum in erythrocytes is well established, the role of Ca2+ in parasite egress is poorly understood. This study analysed the involvement of cytoplasmic free Ca2+ in infected erythrocytes during the multistep egress programme of malaria parasites. Methods Live-cell fluorescence microscopy was used to image parasite egress from infected erythrocytes, assessing the effect of drugs modulating Ca2+ homeostasis on the egress programme. Results A steady increase in cytoplasmic free Ca2+ is found to precede parasite egress. This increase is independent of extracellular Ca2+ for at least the last two hours of the cycle, but is dependent upon Ca2+ release from internal stores. Intracellular BAPTA chelation of Ca2+ within the last 45 minutes of the cycle inhibits egress prior to parasitophorous vacuole swelling and erythrocyte membrane poration, two characteristic morphological transformations preceding parasite egress. Inhibitors of the parasite endoplasmic reticulum (ER Ca2+-ATPase accelerate parasite egress, indicating that Ca2+ stores within the ER are sufficient in supporting egress. Markedly accelerated egress of apparently viable parasites was achieved in mature schizonts using Ca2+ ionophore A23187. Ionophore treatment overcomes the BAPTA-induced block of parasite egress, confirming that free Ca2+ is essential in egress initiation. Ionophore treatment of immature schizonts had an adverse effect inducing parasitophorous vacuole swelling and killing the parasites within the host cell. Conclusions The parasite egress

  16. Host scavenger receptor SR-BI plays a dual role in the establishment of malaria parasite liver infection

    Rodrigues, Cristina D.; Hannus, Michael; Prudencio, Miguel; Martin, Cecilie; Goncalves, Ligia A.; Portugal, Silvia; Epiphanio, Sabrina; Akinc, Akin; Hadwiger, Philipp; Jahn-Hofmann, Kerstin; Roehl, Ingo; van Gemert, Geert-Jan; Franetich, Jean-Francois; Luty, Adrian J. F.; Sauerwein, Robert; Mazier, Dominique; Koteliansky, Victor; Vornlocher, Hans-Peter; Echeverri, Christophe J.; Mota, Maria M.

    2008-01-01

    An obligatory step of malaria parasite infection is Plasmodium sporozoite invasion of host hepatocytes, and host lipoprotein clearance pathways have been linked to Plasmodium liver infection. By using RNA interference to screen lipoprotein-related host factors, we show here that the class B, type I

  17. cAMP-Signalling Regulates Gametocyte-Infected Erythrocyte Deformability Required for Malaria Parasite Transmission.

    Ghania Ramdani

    2015-05-01

    Full Text Available Blocking Plasmodium falciparum transmission to mosquitoes has been designated a strategic objective in the global agenda of malaria elimination. Transmission is ensured by gametocyte-infected erythrocytes (GIE that sequester in the bone marrow and at maturation are released into peripheral blood from where they are taken up during a mosquito blood meal. Release into the blood circulation is accompanied by an increase in GIE deformability that allows them to pass through the spleen. Here, we used a microsphere matrix to mimic splenic filtration and investigated the role of cAMP-signalling in regulating GIE deformability. We demonstrated that mature GIE deformability is dependent on reduced cAMP-signalling and on increased phosphodiesterase expression in stage V gametocytes, and that parasite cAMP-dependent kinase activity contributes to the stiffness of immature gametocytes. Importantly, pharmacological agents that raise cAMP levels in transmissible stage V gametocytes render them less deformable and hence less likely to circulate through the spleen. Therefore, phosphodiesterase inhibitors that raise cAMP levels in P. falciparum infected erythrocytes, such as sildenafil, represent new candidate drugs to block transmission of malaria parasites.

  18. Neglected Parasitic Infections: Toxocariasis

    2012-01-05

    This podcast is an overview of the Clinician Outreach and Communication Activity (COCA) Call: Neglected Parasitic Infections in the United States. Neglected Parasitic Infections are a group of diseases that afflict vulnerable populations and are often not well studied or diagnosed. A subject matter expert from CDC's Division of Parasitic Diseases and Malaria describes the epidemiology, diagnosis, and treatment of toxocariasis.  Created: 1/5/2012 by Center for Global Health, Division of Parasitic Diseases and Malaria (DPDM); Emergency Risk Communication Branch (ERCB)/Joint Information Center (JIC), Office of Public Health Preparedness and Response (OPHPR).   Date Released: 1/9/2012.

  19. Do the mitochondria of malaria parasites behave like the phoenix after return in the mosquito? Regeneration of degenerated mitochondria is required for successful Plasmodium infection.

    Bongaerts, G.P.A.

    2005-01-01

    Mitochondria are energy generators in eukaryotic organisms like man and the pathogenic malaria parasites, the Plasmodium spp. From the moment a mosquito-mediated malaria infection occurs in man the parasite multiplies profusely, but eventually the oxygen supply becomes the limiting factor in this

  20. Do the mitochondria of malaria parasites behave like the phoenix after return in the mosquito? Regeneration of degenerated mitochondria is required for successful Plasmodium infection.

    Bongaerts, Ger

    2005-01-01

    Mitochondria are energy generators in eukaryotic organisms like man and the pathogenic malaria parasites, the Plasmodium spp. From the moment a mosquito-mediated malaria infection occurs in man the parasite multiplies profusely, but eventually the oxygen supply becomes the limiting factor in this process. Consequently, the parasite will increasingly generate energy (and lactic acid) from sugar fermentation. Simultaneously, the cristate structure of Plasmodium mitochondria degenerates and becomes acristate. The degenerated acristate mitochondria of mammalian Plasmodium parasites seem to be able to revitalise by transforming to cristate mitochondria inside the oxygen-rich mosquito, like the rebirth of the old phoenix. In this way the infectivity of the parasite is revitalised.

  1. Experimental evaluation of the relationship between lethal or non-lethal virulence and transmission success in malaria parasite infections

    Nithiuthai S

    2004-09-01

    Full Text Available Abstract Background Evolutionary theory suggests that the selection pressure on parasites to maximize their transmission determines their optimal host exploitation strategies and thus their virulence. Establishing the adaptive basis to parasite life history traits has important consequences for predicting parasite responses to public health interventions. In this study we examine the extent to which malaria parasites conform to the predicted adaptive trade-off between transmission and virulence, as defined by mortality. The majority of natural infections, however, result in sub-lethal virulent effects (e.g. anaemia and are often composed of many strains. Both sub-lethal effects and pathogen population structure have been theoretically shown to have important consequences for virulence evolution. Thus, we additionally examine the relationship between anaemia and transmission in single and mixed clone infections. Results Whereas there was a trade-off between transmission success and virulence as defined by host mortality, contradictory clone-specific patterns occurred when defining virulence by anaemia. A negative relationship between anaemia and transmission success was found for one of the parasite clones, whereas there was no relationship for the other. Notably the two parasite clones also differed in a transmission phenotype (gametocyte sex ratio that has previously been shown to respond adaptively to a changing blood environment. In addition, as predicted by evolutionary theory, mixed infections resulted in increased anaemia. The increased anaemia was, however, not correlated with any discernable parasite trait (e.g. parasite density or with increased transmission. Conclusions We found some evidence supporting the hypothesis that there is an adaptive basis correlating virulence (as defined by host mortality and transmission success in malaria parasites. This confirms the validity of applying evolutionary virulence theory to biomedical

  2. Gammaherpesvirus Co-infection with Malaria Suppresses Anti-parasitic Humoral Immunity.

    Caline G Matar

    2015-05-01

    Full Text Available Immunity to non-cerebral severe malaria is estimated to occur within 1-2 infections in areas of endemic transmission for Plasmodium falciparum. Yet, nearly 20% of infected children die annually as a result of severe malaria. Multiple risk factors are postulated to exacerbate malarial disease, one being co-infections with other pathogens. Children living in Sub-Saharan Africa are seropositive for Epstein Barr Virus (EBV by the age of 6 months. This timing overlaps with the waning of protective maternal antibodies and susceptibility to primary Plasmodium infection. However, the impact of acute EBV infection on the generation of anti-malarial immunity is unknown. Using well established mouse models of infection, we show here that acute, but not latent murine gammaherpesvirus 68 (MHV68 infection suppresses the anti-malarial humoral response to a secondary malaria infection. Importantly, this resulted in the transformation of a non-lethal P. yoelii XNL infection into a lethal one; an outcome that is correlated with a defect in the maintenance of germinal center B cells and T follicular helper (Tfh cells in the spleen. Furthermore, we have identified the MHV68 M2 protein as an important virus encoded protein that can: (i suppress anti-MHV68 humoral responses during acute MHV68 infection; and (ii plays a critical role in the observed suppression of anti-malarial humoral responses in the setting of co-infection. Notably, co-infection with an M2-null mutant MHV68 eliminates lethality of P. yoelii XNL. Collectively, our data demonstrates that an acute gammaherpesvirus infection can negatively impact the development of an anti-malarial immune response. This suggests that acute infection with EBV should be investigated as a risk factor for non-cerebral severe malaria in young children living in areas endemic for Plasmodium transmission.

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

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

    2008-10-01

    Malaria parasites (genus Plasmodium) infect all classes of terrestrial vertebrates and display host specificity in their infections. It is therefore assumed that malaria parasites coevolved intimately with their hosts. Here, we propose a novel scenario of malaria parasite-host coevolution. A phylogenetic tree constructed using the malaria parasite mitochondrial genome reveals that the extant primate, rodent, bird, and reptile parasite lineages rapidly diverged from a common ancestor during an evolutionary short time period. This rapid diversification occurred long after the establishment of the primate, rodent, bird, and reptile host lineages, which implies that host-switch events contributed to the rapid diversification of extant malaria parasite lineages. Interestingly, the rapid diversification coincides with the radiation of the mammalian genera, suggesting that adaptive radiation to new mammalian hosts triggered the rapid diversification of extant malaria parasite lineages.

  4. Expression of senescent antigen on erythrocytes infected with a knobby variant of the human malaria parasite Plasmodium falciparum

    Winograd, E.; Greenan, J.R.T.; Sherman, I.W.

    1987-01-01

    Erythrocytes infected with a knobby variant of Plasmodium falciparum selectively bind IgG autoantibodies in normal human serum. Quantification of membrane-bound IgG, by use of 125 I-labeled protein A, revealed that erythrocytes infected with the knobby variant bound 30 times more protein A than did noninfected erythrocytes; infection with a knobless variant resulted in less than a 2-fold difference compared with noninfected erythrocytes. IgG binding to knobby erythrocytes appeared to be related to parasite development, since binding of 125 I-labeled protein A to cells bearing young trophozoites (less than 20 hr after parasite invasion) was similar to binding to uninfected erythrocytes. By immunoelectron microscopy, the membrane-bound IgG on erythrocytes infected with the knobby variant was found to be preferentially associated with the protuberances (knobs) of the plasma membrane. The removal of aged or senescent erythrocytes from the peripheral circulation is reported to involve the binding of specific antibodies to an antigen (senescent antigen) related to the major erythrocyte membrane protein band 3. Since affinity-purified autoantibodies against band 3 specifically bound to the plasma membrane of erythrocytes infected with the knobby variant of P. falciparum, it is clear that the malaria parasite induces expression of senescent antigen

  5. The Impact of Cooperative Social Organization on Reducing the Prevalence of Malaria and Intestinal Parasite Infections in Awramba, a Rural Community in South Gondar, Ethiopia

    Gebeyehu Yihenew

    2014-01-01

    Full Text Available Introduction. Parasitic diseases are the major causes of human health problem in Ethiopia. The high prevalence of parasitic infections is closely correlated with poverty, poor environmental hygiene, and impoverished health services. Objective. The study was conducted to assess the impact of health-conscious Awramba cooperative community and its neighboring communities on the prevalence of parasitic infections in South Gondar, Ethiopia. Methods. Single stool specimens were collected from 392 individuals from Awramba and the neighboring communities. Specimens were examined microscopically for the presence of parasites using microscopy. Questionnaire was administered to determine the knowledge attitude and practice (KAP of study participants. Results. Of the total 392 study participants examined, 58(14.8% were positive for malaria and 173 (44.1% for intestinal parasites. The prevalence of malaria in Awramba community (5.1% was less than that in neighboring communities (24.5%. The prevalence of parasitic infections in Awramba (18.8% was less than that of the neighboring communities (69.4%. Conclusion. This study showed that good household and environmental hygiene, good toilet construction and usage, and proper utilization of ITN in Awramba cooperative community have significantly contributed to the reduction of the burden of parasitic infections. Thus, the positive achievement in reducing parasitic infections in Awramba cooperative community could be used as a model for affordable health intervention in the neighboring communities, in particular, and the whole country in general.

  6. Optimising Controlled Human Malaria Infection Studies Using Cryopreserved P. falciparum Parasites Administered by Needle and Syringe.

    Susanne H Sheehy

    Full Text Available Controlled human malaria infection (CHMI studies have become a routine tool to evaluate efficacy of candidate anti-malarial drugs and vaccines. To date, CHMI trials have mostly been conducted using the bite of infected mosquitoes, restricting the number of trial sites that can perform CHMI studies. Aseptic, cryopreserved P. falciparum sporozoites (PfSPZ Challenge provide a potentially more accurate, reproducible and practical alternative, allowing a known number of sporozoites to be administered simply by injection.We sought to assess the infectivity of PfSPZ Challenge administered in different dosing regimens to malaria-naive healthy adults (n = 18. Six participants received 2,500 sporozoites intradermally (ID, six received 2,500 sporozoites intramuscularly (IM and six received 25,000 sporozoites IM.Five out of six participants receiving 2,500 sporozoites ID, 3/6 participants receiving 2,500 sporozoites IM and 6/6 participants receiving 25,000 sporozoites IM were successfully infected. The median time to diagnosis was 13.2, 17.8 and 12.7 days for 2,500 sporozoites ID, 2,500 sporozoites IM and 25,000 sporozoites IM respectively (Kaplan Meier method; p = 0.024 log rank test.2,500 sporozoites ID and 25,000 sporozoites IM have similar infectivities. Given the dose response in infectivity seen with IM administration, further work should evaluate increasing doses of PfSPZ Challenge IM to identify a dosing regimen that reliably infects 100% of participants.ClinicalTrials.gov NCT01465048.

  7. Detection of the Malaria causing Plasmodium Parasite in Saliva from Infected Patients using Topoisomerase I Activity as a Biomarker

    Hede, Marianne Smedegaard; Fjelstrup, Søren; Lötsch, Felix

    2018-01-01

    that may be adapted for low-resource settings. Moreover, we demonstrate the exploitation of this assay for detection of malaria in saliva. The setup relies on pump-free microfluidics enabled extraction combined with a DNA sensor substrate that is converted to a single-stranded DNA circle specifically...... (HRP) and addition of 3,3',5,5'-Tetramethylbenzidine that was converted to a blue colored product by HRP. The assay was directly quantitative, specific for Plasmodium parasites, and allowed detection of Plasmodium infection in a single drop of saliva from 35 out of 35 infected individuals tested....... The results could be determined directly by the naked eye and documented by quantifying the color intensity using a standard paper scanner....

  8. Parasitic infections and immune function : Effect of helminth infections in a malaria endemic area

    Boef, Anna G.C.; May, Linda; van Bodegom, David; van Lieshout, Lisette; Verweij, Jaco J.; Maier, Andrea B.; Westendorp, Rudi G.J.; Eriksson, Ulrika K.

    According to the hygiene hypothesis, reduced exposure to infections could explain the rise of atopic diseases in high-income countries. Helminths are hypothesised to alter the host's immune response in order to avoid elimination and, as a consequence, also reduce the host responsiveness to potential

  9. Immune escape strategies of malaria parasites

    Pollyanna Stephanie Gomes

    2016-10-01

    Full Text Available Malaria is one of the most life-threatening infectious diseases worldwide. Immunity to malaria is slow and short-lived despite the repeated parasite exposure in endemic areas. Malaria parasites have evolved refined machinery to evade the immune system based on a range of genetic changes that include allelic variation, biomolecular exposure of proteins and intracellular replication. All of these features increase the probability of survival in both mosquitoes and the vertebrate host. Plasmodium species escape from the first immunological trap in its invertebrate vector host, the Anopheles mosquitoes. The parasites have to pass through various immunological barriers within the mosquito such as anti-microbial molecules and the mosquito microbiota in order to achieve successful transmission to the vertebrate host. Within these hosts, Plasmodium species employ various immune evasion strategies during different life cycle stages. Parasite persistence against the vertebrate immune response depends on the balance among virulence factors, pathology, metabolic cost of the host immune response, and the parasites ability to evade the immune response. In this review we discuss the strategies that Plasmodium parasites use to avoid the vertebrate host immune system and how they promote successful infection and transmission.

  10. Pitting of malaria parasites and spherocyte formation

    Gichuki Charity W

    2006-07-01

    Full Text Available Abstract Background A high prevalence of spherocytes was detected in blood smears of children enrolled in a case control study conducted in the malaria holoendemic Lake Victoria basin. It was speculated that the spherocytes reflect intraerythrocytic removal of malarial parasites with a concurrent removal of RBC membrane through a process analogous to pitting of intraerythrocytic inclusion bodies. Pitting and re-circulation of RBCs devoid of malaria parasites could be a host mechanism for parasite clearance while minimizing the anaemia that would occur were the entire parasitized RBC removed. The prior demonstration of RBCs containing ring-infected erythrocyte surface antigen (pf 155 or RESA but no intracellular parasites, support the idea of pitting. Methods An in vitro model was developed to examine the phenomenon of pitting and spherocyte formation in Plasmodium falciparum infected RBCs (iRBC co-incubated with human macrophages. In vivo application of this model was evaluated using blood specimens from patients attending Kisumu Ditrict Hospital. RBCs were probed with anti-RESA monoclonal antibody and a DNA stain (propidium iodide. Flow cytometry and fluorescent microscopy was used to compare RBCs containing both the antigen and the parasites to those that were only RESA positive. Results Co-incubation of iRBC and tumor necrosis factor-alpha activated macrophages led to pitting (14% ± 1.31% macrophages with engulfed trophozoites as opposed to erythrophagocytosis (5.33% ± 0.95% (P Conclusion It is proposed that in malaria holoendemic areas where prevalence of asexual stage parasites approaches 100% in children, RBCs with pitted parasites are re-circulated and pitting may produce spherocytes.

  11. Prevalence of and risk factors for malaria, filariasis, and intestinal parasites as single infections or co-infections in different settlements of Gabon, Central Africa.

    M'bondoukwé, Noé Patrick; Kendjo, Eric; Mawili-Mboumba, Denise Patricia; Koumba Lengongo, Jeanne Vanessa; Offouga Mbouoronde, Christelle; Nkoghe, Dieudonné; Touré, Fousseyni; Bouyou-Akotet, Marielle Karine

    2018-01-30

    Malaria, filariasis, and intestinal parasitic infections (IPIs) are common and frequently overlap in developing countries. The prevalence and predictors of these infections were investigated in three different settlements (rural, semi-urban, and urban) of Gabon. During cross-sectional surveys performed from September 2013 to June 2014, 451 individuals were interviewed. In addition, blood and stool samples were analysed for the presence of Plasmodium, filarial roundworm, intestinal protozoan, and helminth infections. Intestinal parasitic infections (61.1%), including intestinal protozoa (56.7%) and soil-transmitted helminths (STHs) (22.2%), predominated, whereas Plasmodium falciparum (18.8%), Loa loa (4.7%), and Mansonella perstans (1.1%) were less prevalent. Filariasis and STHs were mainly found in rural settlements, whereas a higher plasmodial infection prevalence rate was observed in the periurban area. The most common IPI was blastocystosis (48.6%), followed by ascaridiasis (13.7%), trichuriasis (11.8%), amoebiasis (9.3%), giardiasis (4.8%), and strongyloidiasis (3.7%). Hookworm was detected in one adult from rural Dienga. Adults had a higher prevalence of Blastocystis hominis and STHs, whereas Giardia duodenalis was more frequently observed among children aged below 5 years (P < 0.01). The polyparasitism rate was 41.5%, with 7.0% Plasmodium-IPIs and 1.8% Plasmodium-STH co-infections. The multivariate analysis showed that living in a suburban area, belonging to the age group of 5-15 years, having none or a secondary education, or having an open body water close to home were significant risk factors for malaria (P ≤ 0.01). For STH infections, identified risk factors were drinking untreated water and living in a rural area (P ≤ 0.04). No significant predictors were identified for IPIs and malaria-IPI co-infection. This study reports a high prevalence of IPIs and intestinal protozoa, but a low rate of malaria-IPI co-infections in the study sites

  12. Malaria parasite-synthesized heme is essential in the mosquito and liver stages and complements host heme in the blood stages of infection.

    Viswanathan Arun Nagaraj

    Full Text Available Heme metabolism is central to malaria parasite biology. The parasite acquires heme from host hemoglobin in the intraerythrocytic stages and stores it as hemozoin to prevent free heme toxicity. The parasite can also synthesize heme de novo, and all the enzymes in the pathway are characterized. To study the role of the dual heme sources in malaria parasite growth and development, we knocked out the first enzyme, δ-aminolevulinate synthase (ALAS, and the last enzyme, ferrochelatase (FC, in the heme-biosynthetic pathway of Plasmodium berghei (Pb. The wild-type and knockout (KO parasites had similar intraerythrocytic growth patterns in mice. We carried out in vitro radiolabeling of heme in Pb-infected mouse reticulocytes and Plasmodium falciparum-infected human RBCs using [4-(14C] aminolevulinic acid (ALA. We found that the parasites incorporated both host hemoglobin-heme and parasite-synthesized heme into hemozoin and mitochondrial cytochromes. The similar fates of the two heme sources suggest that they may serve as backup mechanisms to provide heme in the intraerythrocytic stages. Nevertheless, the de novo pathway is absolutely essential for parasite development in the mosquito and liver stages. PbKO parasites formed drastically reduced oocysts and did not form sporozoites in the salivary glands. Oocyst production in PbALASKO parasites recovered when mosquitoes received an ALA supplement. PbALASKO sporozoites could infect mice only when the mice received an ALA supplement. Our results indicate the potential for new therapeutic interventions targeting the heme-biosynthetic pathway in the parasite during the mosquito and liver stages.

  13. Impact on malaria parasite multiplication rates in infected volunteers of the protein-in-adjuvant vaccine AMA1-C1/Alhydrogel+CPG 7909.

    Christopher J A Duncan

    Full Text Available Inhibition of parasite growth is a major objective of blood-stage malaria vaccines. The in vitro assay of parasite growth inhibitory activity (GIA is widely used as a surrogate marker for malaria vaccine efficacy in the down-selection of candidate blood-stage vaccines. Here we report the first study to examine the relationship between in vivo Plasmodium falciparum growth rates and in vitro GIA in humans experimentally infected with blood-stage malaria.In this phase I/IIa open-label clinical trial five healthy malaria-naive volunteers were immunised with AMA1/C1-Alhydrogel+CPG 7909, and together with three unvaccinated controls were challenged by intravenous inoculation of P. falciparum infected erythrocytes.A significant correlation was observed between parasite multiplication rate in 48 hours (PMR and both vaccine-induced growth-inhibitory activity (Pearson r = -0.93 [95% CI: -1.0, -0.27] P = 0.02 and AMA1 antibody titres in the vaccine group (Pearson r = -0.93 [95% CI: -0.99, -0.25] P = 0.02. However immunisation failed to reduce overall mean PMR in the vaccine group in comparison to the controls (vaccinee 16 fold [95% CI: 12, 22], control 17 fold [CI: 0, 65] P = 0.70. Therefore no impact on pre-patent period was observed (vaccine group median 8.5 days [range 7.5-9], control group median 9 days [range 7-9].Despite the first observation in human experimental malaria infection of a significant association between vaccine-induced in vitro growth inhibitory activity and in vivo parasite multiplication rate, this did not translate into any observable clinically relevant vaccine effect in this small group of volunteers.ClinicalTrials.gov [NCT00984763].

  14. Quantifying Transmission Investment in Malaria Parasites.

    Megan A Greischar

    2016-02-01

    Full Text Available Many microparasites infect new hosts with specialized life stages, requiring a subset of the parasite population to forgo proliferation and develop into transmission forms. Transmission stage production influences infectivity, host exploitation, and the impact of medical interventions like drug treatment. Predicting how parasites will respond to public health efforts on both epidemiological and evolutionary timescales requires understanding transmission strategies. These strategies can rarely be observed directly and must typically be inferred from infection dynamics. Using malaria as a case study, we test previously described methods for inferring transmission stage investment against simulated data generated with a model of within-host infection dynamics, where the true transmission investment is known. We show that existing methods are inadequate and potentially very misleading. The key difficulty lies in separating transmission stages produced by different generations of parasites. We develop a new approach that performs much better on simulated data. Applying this approach to real data from mice infected with a single Plasmodium chabaudi strain, we estimate that transmission investment varies from zero to 20%, with evidence for variable investment over time in some hosts, but not others. These patterns suggest that, even in experimental infections where host genetics and other environmental factors are controlled, parasites may exhibit remarkably different patterns of transmission investment.

  15. HIGH-THROUGHPUT IDENTIFICATION OF THE PREDOMINANT MALARIA PARASITE CLONE IN COMPLEX BLOOD STAGE INFECTIONS USING A MULTI-SNP MOLECULAR HAPLOTYPING ASSAY

    COLE-TOBIAN, JENNIFER L.; ZIMMERMAN, PETER A.; KING, CHRISTOPHER L.

    2013-01-01

    Individuals living in malaria endemic areas are often infected with multiple parasite clones. Currently used single nucleotide polymorphism (SNP) genotyping methods for malaria parasites are cumbersome; furthermore, few methods currently exist that can rapidly determine the most abundant clone in these complex infections. Here we describe an oligonucleotide ligation assay (OLA) to distinguish SNPs in the Plasmodium vivax Duffy binding protein gene (Pvdbp) at 14 polymorphic residues simultaneously. Allele abundance is determined by the highest mean fluorescent intensity of each allele. Using mixtures of plasmids encoding known haplotypes of the Pvdbp, single clones of P. vivax parasites from infected Aotus monkeys, and well-defined mixed infections from field samples, we were able to identify the predominant Pvdbp genotype with > 93% accuracy when the dominant clone is twice as abundant as a lesser genotype and > 97% of the time if the ratio was 5:1 or greater. Thus, the OLA can accurately, reproducibly, and rapidly determine the predominant parasite haplotype in complex blood stage infections. PMID:17255222

  16. Patterns of Infection and Patterns of Evolution: How a Malaria Parasite Brought "Monkeys and Man" Closer Together in the 1960s.

    Mason Dentinger, Rachel

    2016-04-01

    In 1960, American parasitologist Don Eyles was unexpectedly infected with a malariaparasite isolated from a macaque. He and his supervisor, G. Robert Coatney of the National Institutes of Health, had started this series of experiments with the assumption that humans were not susceptible to "monkey malaria." The revelation that a mosquito carrying a macaque parasite could infect a human raised a whole range of public health and biological questions. This paper follows Coatney's team of parasitologists and their subjects: from the human to the nonhuman; from the American laboratory to the forests of Malaysia; and between the domains of medical research and natural history. In the course of this research, Coatney and his colleagues inverted Koch's postulate, by which animal subjects are used to identify and understand human parasites. In contrast, Coatney's experimental protocol used human subjects to identify and understand monkey parasites. In so doing, the team repeatedly followed malaria parasites across the purported boundary separating monkeys and humans, a practical experience that created a sense of biological symmetry between these separate species. Ultimately, this led Coatney and his colleagues make evolutionary inferences, concluding "that monkeys and man are more closely related than some of us wish to admit." In following monkeys, men, and malaria across biological, geographical, and disciplinary boundaries, this paper offers a new historical narrative, demonstrating that the pursuit of public health agendas can fuel the expansion of evolutionary knowledge.

  17. Host-seeking behaviors of mosquitoes experimentally infected with sympatric field isolates of the human malaria parasite Plasmodium falciparum: no evidence for host manipulation

    Amélie eVantaux

    2015-08-01

    Full Text Available Previous studies have shown that Plasmodium parasites can manipulate mosquito feeding behaviours such as motivation and avidity to feed on vertebrate hosts, in ways that increase the probability of parasite transmission. These studies, however, have been mainly carried out on non-natural and/or laboratory based model systems and hence may not reflect what occurs in the field. We now need to move closer to the natural setting, if we are to fully capture the ecological and evolutionary consequences of these parasite-induced behavioral changes. As part of this effort, we conducted a series of experiments to investigate the long and short-range behavioural responses to human stimuli in the mosquito Anopheles coluzzii during different stages of infection with sympatric field isolates of the human malaria parasite Plasmodium falciparum in Burkina Faso. First, we used a dual-port olfactometer designed to take advantage of the whole body odor to gauge mosquito long-range host-seeking behaviors. Second, we used a locomotor activity monitor system to assess mosquito short-range behaviors. Compared to control uninfected mosquitoes, P. falciparum infection had no significant effect neither on long-range nor on short-range behaviors both at the immature and mature stages. This study, using a natural mosquito-malaria parasite association, indicates that manipulation of vector behavior may not be a general phenomenon. We speculate that the observed contrasting phenotypes with model systems might result from coevolution of the human parasite and its natural vector. Future experiments, using other sympatric malaria mosquito populations or species are required to test this hypothesis. In conclusion, our results highlight the importance of following up discoveries in laboratory model systems with studies on natural parasite–mosquito interactions to accurately predict the epidemiological, ecological and evolutionary consequences of parasite manipulation of vector

  18. Rodent malaria parasites : genome organization & comparative genomics

    Kooij, Taco W.A.

    2006-01-01

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

  19. Protein kinase C-dependent signaling controls the midgut epithelial barrier to malaria parasite infection in anopheline mosquitoes.

    Nazzy Pakpour

    Full Text Available Anopheline mosquitoes are the primary vectors of parasites in the genus Plasmodium, the causative agents of malaria. Malaria parasites undergo a series of complex transformations upon ingestion by the mosquito host. During this process, the physical barrier of the midgut epithelium, along with innate immune defenses, functionally restrict parasite development. Although these defenses have been studied for some time, the regulatory factors that control them are poorly understood. The protein kinase C (PKC gene family consists of serine/threonine kinases that serve as central signaling molecules and regulators of a broad spectrum of cellular processes including epithelial barrier function and immunity. Indeed, PKCs are highly conserved, ranging from 7 isoforms in Drosophila to 16 isoforms in mammals, yet none have been identified in mosquitoes. Despite conservation of the PKC gene family and their potential as targets for transmission-blocking strategies for malaria, no direct connections between PKCs, the mosquito immune response or epithelial barrier integrity are known. Here, we identify and characterize six PKC gene family members--PKCδ, PKCε, PKCζ, PKD, PKN, and an indeterminate conventional PKC--in Anopheles gambiae and Anopheles stephensi. Sequence and phylogenetic analyses of the anopheline PKCs support most subfamily assignments. All six PKCs are expressed in the midgut epithelia of A. gambiae and A. stephensi post-blood feeding, indicating availability for signaling in a tissue that is critical for malaria parasite development. Although inhibition of PKC enzymatic activity decreased NF-κB-regulated anti-microbial peptide expression in mosquito cells in vitro, PKC inhibition had no effect on expression of a panel of immune genes in the midgut epithelium in vivo. PKC inhibition did, however, significantly increase midgut barrier integrity and decrease development of P. falciparum oocysts in A. stephensi, suggesting that PKC

  20. Prevalence of malaria parasites and Hepatitis-B virus in patients ...

    Malaria and Hepatitis-B virus (HBV) remain a threat to human health in many developing nations. Many regions with high malaria prevalence are also endemic for other infectious diseases which may predispose them to more of the malaria infection. Using thin and thick film preparations, malaria parasites were detected, ...

  1. Transformation of the rodent malaria parasite Plasmodium chabaudi.

    Spence, Philip J; Cunningham, Deirdre; Jarra, William; Lawton, Jennifer; Langhorne, Jean; Thompson, Joanne

    2011-04-01

    The rodent malaria parasite Plasmodium chabaudi chabaudi shares many features with human malaria species, including P. falciparum, and is the in vivo model of choice for many aspects of malaria research in the mammalian host, from sequestration of parasitized erythrocytes, to antigenic variation and host immunity and immunopathology. This protocol describes an optimized method for the transformation of mature blood-stage P.c. chabaudi and a description of a vector that targets efficient, single crossover integration into the P.c. chabaudi genome. Transformed lines are reproducibly generated and selected within 14-20 d, and show stable long-term protein expression even in the absence of drug selection. This protocol, therefore, provides the scientific community with a robust and reproducible method to generate transformed P.c. chabaudi parasites expressing fluorescent, bioluminescent and model antigens that can be used in vivo to dissect many of the fundamental principles of malaria infection.

  2. Do the venous blood samples replicate malaria parasite densities found in capillary blood? A field study performed in naturally-infected asymptomatic children in Cameroon.

    Sandeu, Maurice M; Bayibéki, Albert N; Tchioffo, Majoline T; Abate, Luc; Gimonneau, Geoffrey; Awono-Ambéné, Parfait H; Nsango, Sandrine E; Diallo, Diadier; Berry, Antoine; Texier, Gaétan; Morlais, Isabelle

    2017-08-17

    The measure of new drug- or vaccine-based approaches for malaria control is based on direct membrane feeding assays (DMFAs) where gametocyte-infected blood samples are offered to mosquitoes through an artificial feeder system. Gametocyte donors are identified by the microscopic detection and quantification of malaria blood stages on blood films prepared using either capillary or venous blood. However, parasites are known to sequester in the microvasculature and this phenomenon may alter accurate detection of parasites in blood films. The blood source may then impact the success of mosquito feeding experiments and investigations are needed for the implementation of DMFAs under natural conditions. Thick blood smears were prepared from blood obtained from asymptomatic children attending primary schools in the vicinity of Mfou (Cameroon) over four transmission seasons. Parasite densities were determined microscopically from capillary and venous blood for 137 naturally-infected gametocyte carriers. The effect of the blood source on gametocyte and asexual stage densities was then assessed by fitting cumulative link mixed models (CLMM). DMFAs were performed to compare the infectiousness of gametocytes from the different blood sources to mosquitoes. Prevalence of Plasmodium falciparum asexual stages among asymptomatic children aged from 4 to 15 years was 51.8% (2116/4087). The overall prevalence of P. falciparum gametocyte carriage was 8.9% and varied from one school to another. No difference in the density of gametocyte and asexual stages was found between capillary and venous blood. Attempts to perform DMFAs with capillary blood failed. Plasmodium falciparum malaria parasite densities do not differ between capillary and venous blood in asymptomatic subjects for both gametocyte and trophozoite stages. This finding suggests that the blood source should not interfere with transmission efficiency in DMFAs.

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

    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.

  4. Early gametocytes of the malaria parasite Plasmodium falciparum specifically remodel the adhesive properties of infected erythrocyte surface

    Tibúrcio, Marta; Silvestrini, Francesco; Bertuccini, Lucia

    2013-01-01

    to ultrastructurally and biochemically analyse parasite-induced modifications on the red blood cell surface and to measure their functional consequences on adhesion to human endothelial cells. This work revealed that stage I gametocytes are able to deform the infected erythrocytes like asexual parasites, but do...... not modify its surface with adhesive 'knob' structures and associated proteins. Reduced levels of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesins are exposed on the red blood cell surface bythese parasites, and the expression of the var gene family, which encodes 50-60 variants of PfEMP1......In Plasmodium falciparum infections the parasite transmission stages, the gametocytes, mature in 10 days sequestered in internal organs. Recent studies suggest that cell mechanical properties rather than adhesive interactions play a role in sequestration during gametocyte maturation. It remains...

  5. Immunity to parasitic infection

    Lamb, Tracey J

    2012-01-01

    ... may be manipulated to develop therapeutic interventions against parasitic infection. For easy reference, the most commonly studied parasites are examined in individual chapters written by investigators at the forefront of their field...

  6. A Feast of Malaria Parasite Genomes.

    Carlton, Jane M; Sullivan, Steven A

    2017-03-08

    The Plasmodium genus has evolved over time and across hosts, complexifying our understanding of malaria. In a recent Nature paper, Rutledge et al. (2017) describe the genome sequences of three major human malaria parasite species, providing insight into Plasmodium evolution and raising the question of how many species there are. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. A large proportion of asymptomatic Plasmodium infections with low and sub-microscopic parasite densities in the low transmission setting of Temotu Province, Solomon Islands: challenges for malaria diagnostics in an elimination setting

    Harris Ivor

    2010-09-01

    Full Text Available Abstract Background Many countries are scaling up malaria interventions towards elimination. This transition changes demands on malaria diagnostics from diagnosing ill patients to detecting parasites in all carriers including asymptomatic infections and infections with low parasite densities. Detection methods suitable to local malaria epidemiology must be selected prior to transitioning a malaria control programme to elimination. A baseline malaria survey conducted in Temotu Province, Solomon Islands in late 2008, as the first step in a provincial malaria elimination programme, provided malaria epidemiology data and an opportunity to assess how well different diagnostic methods performed in this setting. Methods During the survey, 9,491 blood samples were collected and examined by microscopy for Plasmodium species and density, with a subset also examined by polymerase chain reaction (PCR and rapid diagnostic tests (RDTs. The performances of these diagnostic methods were compared. Results A total of 256 samples were positive by microscopy, giving a point prevalence of 2.7%. The species distribution was 17.5% Plasmodium falciparum and 82.4% Plasmodium vivax. In this low transmission setting, only 17.8% of the P. falciparum and 2.9% of P. vivax infected subjects were febrile (≥38°C at the time of the survey. A significant proportion of infections detected by microscopy, 40% and 65.6% for P. falciparum and P. vivax respectively, had parasite density below 100/μL. There was an age correlation for the proportion of parasite density below 100/μL for P. vivax infections, but not for P. falciparum infections. PCR detected substantially more infections than microscopy (point prevalence of 8.71%, indicating a large number of subjects had sub-microscopic parasitemia. The concordance between PCR and microscopy in detecting single species was greater for P. vivax (135/162 compared to P. falciparum (36/118. The malaria RDT detected the 12 microscopy and

  8. Malaria parasite positivity among febrile neonates | Enyuma ...

    Background: Malaria, earlier considered rare in neonates, has been reported with increasing frequency in the last decade. Neonatal malaria diagnosis is challenging because the clinical features are non-specific, variable and also overlap with bacterial infection. Aim: To determine the prevalence of neonatal malaria and ...

  9. Mosquito transmission of the rodent malaria parasite Plasmodium chabaudi

    Spence Philip J

    2012-12-01

    Full Text Available Abstract Background Serial blood passage of Plasmodium increases virulence, whilst mosquito transmission inherently regulates parasite virulence within the mammalian host. It is, therefore, imperative that all aspects of experimental malaria research are studied in the context of the complete Plasmodium life cycle. Methods Plasmodium chabaudi chabaudi displays many characteristics associated with human Plasmodium infection of natural mosquito vectors and the mammalian host, and thus provides a unique opportunity to study the pathogenesis of malaria in a single infection setting. An optimized protocol that permits efficient and reproducible vector transmission of P. c. chabaudi via Anopheles stephensi was developed. Results and conclusions This protocol was utilized for mosquito transmission of genetically distinct P. c. chabaudi isolates, highlighting differential parasite virulence within the mosquito vector and the spectrum of host susceptibility to infection initiated via the natural route, mosquito bite. An apposite experimental system in which to delineate the pathogenesis of malaria is described in detail.

  10. The distinct proteome of placental malaria parasites.

    Fried, Michal; Hixson, Kim K.; Anderson, Lori; Ogata, Yuko; Mutabingwa, Theonest K.; Duffy, Patrick E.

    2007-09-01

    Malaria proteins expressed on the surface of Plasmodium falciparum infected erythrocytes (IE) mediate adhesion and are targeted by protective immune responses. During pregnancy, IE sequester in the placenta. Placental IE bind to the molecule chondroitin sulfate A (CSA) and preferentially transcribe the gene that encodes VAR2CSA, a member of the PfEMP1 variant surface antigen family. Over successive pregnancies women develop specific immunity to CSA-binding IE and antibodies to VAR2CSA. We used tandem mass spectrometry together with accurate mass and time tag technology to study IE membrane fractions of placental parasites. VAR2CSA peptides were detected in placental IE and in IE from children, but the MC variant of VAR2CSA was specifically associated with placental IE. We identified six conserved hypothetical proteins with putative TM or signal peptides that were exclusively expressed by the placental IE, and 11 such proteins that were significantly more abundant in placental IE. One of these hypothetical proteins, PFI1785w, is a 42kDa molecule detected by Western blot in parasites infecting pregnant women but not those infecting children.

  11. Malaria Parasite CLAG3, a Protein Linked to Nutrient Channels, Participates in High Molecular Weight Membrane-Associated Complexes in the Infected Erythrocyte.

    Kayvan Zainabadi

    Full Text Available Malaria infected erythrocytes show increased permeability to a number of solutes important for parasite growth as mediated by the Plasmodial Surface Anion Channel (PSAC. The P. falciparum clag3 genes have recently been identified as key determinants of PSAC, though exactly how they contribute to channel function and whether additional host/parasite proteins are required remain unknown. To begin to answer these questions, I have taken a biochemical approach. Here I have used an epitope-tagged CLAG3 parasite to perform co-immunoprecipitation experiments using membrane fractions of infected erythrocytes. Native PAGE and mass spectrometry studies reveal that CLAG3 participate in at least three different high molecular weight complexes: a ~720kDa complex consisting of CLAG3, RHOPH2 and RHOPH3; a ~620kDa complex consisting of CLAG3 and RHOPH2; and a ~480kDa complex composed solely of CLAG3. Importantly, these complexes can be found throughout the parasite lifecycle but are absent in untransfected controls. Extracellular biotin labeling and protease susceptibility studies localize the 480kDa complex to the erythrocyte membrane. This complex, likely composed of a homo-oligomer of 160kDa CLAG3, may represent a functional subunit, possibly the pore, of PSAC.

  12. Signalling in malaria parasites. The MALSIG consortium.

    Doerig, C.; Baker, D.; Billker, O.; Blackman, M.J.; Chitnis, C.; Dhar Kumar, S.; Heussler, V.; Holder, A.A.; Kocken, C.; Krishna, S.; Langsley, G.; Lasonder, E.; Menard, R.; Meissner, M.; Pradel, G.; Ranford-Cartwright, L.; Sharma, A.; Sharma, P.; Tardieux, T.; Tatu, U.; Alano, P.

    2009-01-01

    Depending on their developmental stage in the life cycle, malaria parasites develop within or outside host cells, and in extremely diverse contexts such as the vertebrate liver and blood circulation, or the insect midgut and hemocoel. Cellular and molecular mechanisms enabling the parasite to sense

  13. Host-parasite interactions and ecology of the malaria parasite-a bioinformatics approach.

    Izak, Dariusz; Klim, Joanna; Kaczanowski, Szymon

    2018-04-25

    Malaria remains one of the highest mortality infectious diseases. Malaria is caused by parasites from the genus Plasmodium. Most deaths are caused by infections involving Plasmodium falciparum, which has a complex life cycle. Malaria parasites are extremely well adapted for interactions with their host and their host's immune system and are able to suppress the human immune system, erase immunological memory and rapidly alter exposed antigens. Owing to this rapid evolution, parasites develop drug resistance and express novel forms of antigenic proteins that are not recognized by the host immune system. There is an emerging need for novel interventions, including novel drugs and vaccines. Designing novel therapies requires knowledge about host-parasite interactions, which is still limited. However, significant progress has recently been achieved in this field through the application of bioinformatics analysis of parasite genome sequences. In this review, we describe the main achievements in 'malarial' bioinformatics and provide examples of successful applications of protein sequence analysis. These examples include the prediction of protein functions based on homology and the prediction of protein surface localization via domain and motif analysis. Additionally, we describe PlasmoDB, a database that stores accumulated experimental data. This tool allows data mining of the stored information and will play an important role in the development of malaria science. Finally, we illustrate the application of bioinformatics in the development of population genetics research on malaria parasites, an approach referred to as reverse ecology.

  14. Malaria rapid diagnostic tests: Plasmodium falciparum infections with high parasite densities may generate false positive Plasmodium vivax pLDH lines

    van Esbroeck Marjan

    2010-07-01

    Full Text Available Abstract Background Most malaria rapid diagnostic tests (RDTs detect Plasmodium falciparum and an antigen common to the four species. Plasmodium vivax-specific RDTs target P. vivax-specific parasite lactate dehydrogenase (Pv-pLDH. Previous observations of false positive Pv-pLDH test lines in P. falciparum samples incited to the present study, which assessed P. vivax-specific RDTs for the occurrence of false positive Pv-pLDH lines in P. falciparum samples. Methods Nine P. vivax-specific RDTs were tested with 85 P. falciparum samples of high (≥2% parasite density. Mixed P. falciparum/P. vivax infections were ruled out by real-time PCR. The RDTs included two-band (detecting Pv-pLDH, three-band (detecting P. falciparum-antigen and Pv-pLDH and four-band RDTs (detecting P. falciparum, Pv-pLDH and pan-pLDH. Results False positive Pv-pLDH lines were observed in 6/9 RDTs (including two- three- and four-band RDTs. They occurred in the individual RDT brands at frequencies ranging from 8.2% to 29.1%. For 19/85 samples, at least two RDT brands generated a false positive Pv-pLDH line. Sixteen of 85 (18.8% false positive lines were of medium or strong line intensity. There was no significant relation between false positive results and parasite density or geographic origin of the samples. Conclusion False positive Pv-pLDH lines in P. falciparum samples with high parasite density occurred in 6/9 P. vivax-specific RDTs. This is of concern as P. falciparum and P. vivax are co-circulating in many regions. The diagnosis of life-threatening P. falciparum malaria may be missed (two-band Pv-pLDH RDT, or the patient may be treated incorrectly with primaquine (three- or four-band RDTs.

  15. Malaria parasites: the great escape

    Laurent Rénia

    2016-11-01

    Full Text Available Parasites of the genus Plasmodium have a complex life cycle. They alternate between their final mosquito host and their intermediate hosts. The parasite can be either extra- or intracellular, depending on the stage of development. By modifying their shape, motility, and metabolic requirements, the parasite adapts to the different environments in their different hosts. The parasite has evolved to escape the multiple immune mechanisms in the host that try to block parasite development at the different stages of their development. In this article, we describe the mechanisms reported thus far that allow the Plasmodium parasite to evade innate and adaptive immune responses.

  16. Plasma antibodies from malaria-exposed pregnant women recognize variant surface antigens on Plasmodium falciparum-infected erythrocytes in a parity-dependent manner and block parasite adhesion to chondroitin sulfate A

    Ricke, C H; Staalsoe, T; Koram, K

    2000-01-01

    -associated malaria (PAM) in endemic areas is concentrated in the first few pregnancies, indicating that protective immunity to PAM is a function of parity. The placenta is often heavily infected in PAM, and placental parasites show a striking preference for chondroitin sulfate A (CSA) as an adhesion receptor. Plasma...

  17. A re-assessment of gene-tag classification approaches for describing var gene expression patterns during human Plasmodium falciparum malaria parasite infections.

    Githinji, George; Bull, Peter C

    2017-01-01

    PfEMP1 are variant parasite antigens that are inserted on the surface of Plasmodium falciparum infected erythrocytes (IE). Through interactions with various host molecules, PfEMP1 mediate IE sequestration in tissues and play a key role in the pathology of severe malaria. PfEMP1 is encoded by a diverse multi-gene family called var . Previous studies have shown that that expression of specific subsets of var genes are associated with low levels of host immunity and severe malaria. However, in most clinical studies to date, full-length var gene sequences were unavailable and various approaches have been used to make comparisons between var gene expression profiles in different parasite isolates using limited information. Several studies have relied on the classification of a 300 - 500 base-pair "DBLα tag" region in the DBLα domain located at the 5' end of most var genes. We assessed the relationship between various DBLα tag classification methods, and sequence features that are only fully assessable through full-length var gene sequences. We compared these different sequence features in full-length var gene from six fully sequenced laboratory isolates. These comparisons show that despite a long history of recombination,   DBLα sequence tag classification can provide functional information on important features of full-length var genes. Notably, a specific subset of DBLα tags previously defined as "group A-like" is associated with CIDRα1 domains proposed to bind to endothelial protein C receptor. This analysis helps to bring together different sources of data that have been used to assess var gene expression in clinical parasite isolates.

  18. Helminth parasites alter protection against Plasmodium infection.

    Salazar-Castañon, Víctor H; Legorreta-Herrera, Martha; Rodriguez-Sosa, Miriam

    2014-01-01

    More than one-third of the world's population is infected with one or more helminthic parasites. Helminth infections are prevalent throughout tropical and subtropical regions where malaria pathogens are transmitted. Malaria is the most widespread and deadliest parasitic disease. The severity of the disease is strongly related to parasite density and the host's immune responses. Furthermore, coinfections between both parasites occur frequently. However, little is known regarding how concomitant infection with helminths and Plasmodium affects the host's immune response. Helminthic infections are frequently massive, chronic, and strong inductors of a Th2-type response. This implies that infection by such parasites could alter the host's susceptibility to subsequent infections by Plasmodium. There are a number of reports on the interactions between helminths and Plasmodium; in some, the burden of Plasmodium parasites increased, but others reported a reduction in the parasite. This review focuses on explaining many of these discrepancies regarding helminth-Plasmodium coinfections in terms of the effects that helminths have on the immune system. In particular, it focuses on helminth-induced immunosuppression and the effects of cytokines controlling polarization toward the Th1 or Th2 arms of the immune response.

  19. Polyamine uptake by the intraerythrocytic malaria parasite, Plasmodium falciparum.

    Niemand, J; Louw, A I; Birkholtz, L; Kirk, K

    2012-09-01

    Polyamines and the enzymes involved in their biosynthesis are present at high levels in rapidly proliferating cells, including cancer cells and protozoan parasites. Inhibition of polyamine biosynthesis in asexual blood-stage malaria parasites causes cytostatic arrest of parasite development under in vitro conditions, but does not cure infections in vivo. This may be due to replenishment of the parasite's intracellular polyamine pool via salvage of exogenous polyamines from the host. However, the mechanism(s) of polyamine uptake by the intraerythrocytic parasite are not well understood. In this study, the uptake of the polyamines, putrescine and spermidine, into Plasmodium falciparum parasites functionally isolated from their host erythrocyte was investigated using radioisotope flux techniques. Both putrescine and spermidine were taken up into isolated parasites via a temperature-dependent process that showed cross-competition between different polyamines. There was also some inhibition of polyamine uptake by basic amino acids. Inhibition of polyamine biosynthesis led to an increase in the total amount of putrescine and spermidine taken up from the extracellular medium. The uptake of putrescine and spermidine by isolated parasites was independent of extracellular Na(+) but increased with increasing external pH. Uptake also showed a marked dependence on the parasite's membrane potential, decreasing with membrane depolarization and increasing with membrane hyperpolarization. The data are consistent with polyamines being taken up into the parasite via an electrogenic uptake process, energised by the parasite's inwardly negative membrane potential. Copyright © 2012 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

  20. African origin of the malaria parasite Plasmodium vivax.

    Liu, Weimin; Li, Yingying; Shaw, Katharina S; Learn, Gerald H; Plenderleith, Lindsey J; Malenke, Jordan A; Sundararaman, Sesh A; Ramirez, Miguel A; Crystal, Patricia A; Smith, Andrew G; Bibollet-Ruche, Frederic; Ayouba, Ahidjo; Locatelli, Sabrina; Esteban, Amandine; Mouacha, Fatima; Guichet, Emilande; Butel, Christelle; Ahuka-Mundeke, Steve; Inogwabini, Bila-Isia; Ndjango, Jean-Bosco N; Speede, Sheri; Sanz, Crickette M; Morgan, David B; Gonder, Mary K; Kranzusch, Philip J; Walsh, Peter D; Georgiev, Alexander V; Muller, Martin N; Piel, Alex K; Stewart, Fiona A; Wilson, Michael L; Pusey, Anne E; Cui, Liwang; Wang, Zenglei; Färnert, Anna; Sutherland, Colin J; Nolder, Debbie; Hart, John A; Hart, Terese B; Bertolani, Paco; Gillis, Amethyst; LeBreton, Matthew; Tafon, Babila; Kiyang, John; Djoko, Cyrille F; Schneider, Bradley S; Wolfe, Nathan D; Mpoudi-Ngole, Eitel; Delaporte, Eric; Carter, Richard; Culleton, Richard L; Shaw, George M; Rayner, Julian C; Peeters, Martine; Hahn, Beatrice H; Sharp, Paul M

    2014-01-01

    Plasmodium vivax is the leading cause of human malaria in Asia and Latin America but is absent from most of central Africa due to the near fixation of a mutation that inhibits the expression of its receptor, the Duffy antigen, on human erythrocytes. The emergence of this protective allele is not understood because P. vivax is believed to have originated in Asia. Here we show, using a non-invasive approach, that wild chimpanzees and gorillas throughout central Africa are endemically infected with parasites that are closely related to human P. vivax. Sequence analyses reveal that ape parasites lack host specificity and are much more diverse than human parasites, which form a monophyletic lineage within the ape parasite radiation. These findings indicate that human P. vivax is of African origin and likely selected for the Duffy-negative mutation. All extant human P. vivax parasites are derived from a single ancestor that escaped out of Africa.

  1. African origin of the malaria parasite Plasmodium vivax

    Liu, Weimin; Li, Yingying; Shaw, Katharina S.; Learn, Gerald H.; Plenderleith, Lindsey J.; Malenke, Jordan A.; Sundararaman, Sesh A.; Ramirez, Miguel A.; Crystal, Patricia A.; Smith, Andrew G.; Bibollet-Ruche, Frederic; Ayouba, Ahidjo; Locatelli, Sabrina; Esteban, Amandine; Mouacha, Fatima; Guichet, Emilande; Butel, Christelle; Ahuka-Mundeke, Steve; Inogwabini, Bila-Isia; Ndjango, Jean-Bosco N.; Speede, Sheri; Sanz, Crickette M.; Morgan, David B.; Gonder, Mary K.; Kranzusch, Philip J.; Walsh, Peter D.; Georgiev, Alexander V.; Muller, Martin N.; Piel, Alex K.; Stewart, Fiona A.; Wilson, Michael L.; Pusey, Anne E.; Cui, Liwang; Wang, Zenglei; Färnert, Anna; Sutherland, Colin J.; Nolder, Debbie; Hart, John A.; Hart, Terese B.; Bertolani, Paco; Gillis, Amethyst; LeBreton, Matthew; Tafon, Babila; Kiyang, John; Djoko, Cyrille F.; Schneider, Bradley S.; Wolfe, Nathan D.; Mpoudi-Ngole, Eitel; Delaporte, Eric; Carter, Richard; Culleton, Richard L.; Shaw, George M.; Rayner, Julian C.; Peeters, Martine; Hahn, Beatrice H.; Sharp, Paul M.

    2014-01-01

    Plasmodium vivax is the leading cause of human malaria in Asia and Latin America but is absent from most of central Africa due to the near fixation of a mutation that inhibits the expression of its receptor, the Duffy antigen, on human erythrocytes. The emergence of this protective allele is not understood because P. vivax is believed to have originated in Asia. Here we show, using a non-invasive approach, that wild chimpanzees and gorillas throughout central Africa are endemically infected with parasites that are closely related to human P. vivax. Sequence analyses reveal that ape parasites lack host specificity and are much more diverse than human parasites, which form a monophyletic lineage within the ape parasite radiation. These findings indicate that human P. vivax is of African origin and likely selected for the Duffy-negative mutation. All extant human P. vivax parasites are derived from a single ancestor that escaped out of Africa. PMID:24557500

  2. Enhanced Transmission of Drug-Resistant Parasites to Mosquitoes following Drug Treatment in Rodent Malaria

    Bell, Andrew S.; Huijben, Silvie; Paaijmans, Krijn P.; Sim, Derek G.; Chan, Brian H. K.; Nelson, William A.; Read, Andrew F.

    2012-01-01

    The evolution of drug resistant Plasmodium parasites is a major challenge to effective malaria control. In theory, competitive interactions between sensitive parasites and resistant parasites within infections are a major determinant of the rate at which parasite evolution undermines drug efficacy. Competitive suppression of resistant parasites in untreated hosts slows the spread of resistance; competitive release following treatment enhances it. Here we report that for the murine model Plasm...

  3. Application of molecular methods for monitoring transmission stages of malaria parasites

    Babiker, Hamza A; Schneider, Petra

    2008-01-01

    Recent technical advances in malaria research have allowed specific detection of mRNA of genes that are expressed exclusively in sexual stages (gametocytes) of malaria parasites. The specificity and sensitivity of these techniques were validated on cultured laboratory clones of both human malaria parasites (Plasmodium falciparum) and rodent parasites (P. chabaudi). More recently, quantitative molecular techniques have been developed to quantify these sexual stages and used to monitor gametocyte dynamics and their transmission to mosquitoes. Molecular techniques showed that the infectious reservoir for malaria is larger than expected from previous microscopic studies; individual parasite genotypes within an infection can simultaneously produce infectious gametocytes; gametocyte production can be sustained for several months, and is modulated by environmental factors. The above techniques have empowered approaches for in-depth analysis of the biology of the transmission stages of the parasite and epidemiology of malaria transmission

  4. From malaria parasite point of view – Plasmodium falciparum evolution

    Agata Zerka

    2015-12-01

    Full Text Available 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.

  5. Parasite Infection, Carcinogenesis and Human Malignancy

    Hoang van Tong

    2017-02-01

    Full Text Available Cancer may be induced by many environmental and physiological conditions. Infections with viruses, bacteria and parasites have been recognized for years to be associated with human carcinogenicity. Here we review current concepts of carcinogenicity and its associations with parasitic infections. The helminth diseases schistosomiasis, opisthorchiasis, and clonorchiasis are highly carcinogenic while the protozoan Trypanosoma cruzi, the causing agent of Chagas disease, has a dual role in the development of cancer, including both carcinogenic and anticancer properties. Although malaria per se does not appear to be causative in carcinogenesis, it is strongly associated with the occurrence of endemic Burkitt lymphoma in areas holoendemic for malaria. The initiation of Plasmodium falciparum related endemic Burkitt lymphoma requires additional transforming events induced by the Epstein-Barr virus. Observations suggest that Strongyloides stercoralis may be a relevant co-factor in HTLV-1-related T cell lymphomas. This review provides an overview of the mechanisms of parasitic infection-induced carcinogenicity.

  6. Associations between maternal helminth and malaria infections in pregnancy, and clinical malaria in the offspring

    Ndibazza, Juliet; Webb, Emily L; Lule, Swaib

    2013-01-01

    Background. Helminth and malaria coinfections are common in the tropics. We investigated the hypothesis that prenatal exposure to these parasites might influence susceptibility to infections such as malaria in childhood.Methods. In a birth cohort of 2,345 mother-child pairs in Uganda, maternal...... helminth and malaria infection status was determined during pregnancy, and childhood malaria episodes recorded from birth to age five years. We examined associations between maternal infections and malaria in the offspring.Results. Common maternal infections were hookworm (45%), Mansonella perstans (21......%), Schistosoma mansoni (18%), and Plasmodium falciparum (11%). At age 5 years, 69% of the children were still under follow-up. The incidence of malaria was 34 episodes per 100 child-years, and the mean prevalence of asymptomatic malaria at annual visits was 5.4%. Maternal hookworm and M. perstans infections were...

  7. PARASITIC INFECTIONS IN HEMATOPOIETIC STEM CELL TRANSPLANTATION

    Isidro Jarque

    2016-07-01

    Full Text Available Parasitic infections are rarely documented in hematopoietic stem cell transplant recipients. However, they may be responsible for fatal complications that are only diagnosed at autopsy. Increased awareness of the possibility of parasitic diseases both in autologous and allogeneic stem cell transplant patients is relevant not only for implementing preventive measures but also for performing an early diagnosis and starting appropriate therapy for these unrecognized but fatal infectious complications in hematopoietic transplant recipients. In this review, we will focus on parasitic diseases occurring in this population especially those with major clinical relevance including toxoplasmosis, American trypanosomiasis, leishmaniasis, malaria, and strongyloidiasis, among others, highlighting the diagnosis and management in hematopoietic transplant recipients.

  8. Malaria and intestinal parasites in pregnant and non-pregnant women

    In sub-Sahara African countries, both malaria and intestinal helminth infections are endemic and co-infection commonly occurs. It is estimated that over a third of the world's population, mainly in the tropics and sub-tropics are infected with parasitic helminths and Plasmodium species thus often leading to co-infections.

  9. Effect of HIV and malaria parasites co-infection on immune-hematological profiles among patients attending anti-retroviral treatment (ART clinic in Infectious Disease Hospital Kano, Nigeria.

    Feyisayo Ebenezer Jegede

    Full Text Available Human immunodeficiency virus (HIV and malaria co-infection may present worse health outcomes in the tropics. Information on HIV/malaria co-infection effect on immune-hematological profiles is critical for patient care and there is a paucity of such data in Nigeria.To evaluate immune-hematological profiles among HIV infected patients compared to HIV/malaria co-infected for ART management improvement.This was a cross sectional study conducted at Infectious Disease Hospital, Kano. A total of 761 consenting adults attending ART clinic were randomly selected and recruited between June and December 2015. Participants' characteristics and clinical details including two previous CD4 counts were collected. Venous blood sample (4ml was collected in EDTA tube for malaria parasite diagnosis by rapid test and confirmed with microscopy. Hematological profiles were analyzed by Sysmex XP-300 and CD4 count by Cyflow cytometry. Data was analyzed with SPSS 22.0 using Chi-Square test for association between HIV/malaria parasites co-infection with age groups, gender, ART, cotrimoxazole and usage of treated bed nets. Mean hematological profiles by HIV/malaria co-infection and HIV only were compared using independent t-test and mean CD4 count tested by mixed design repeated measures ANOVA. Statistical significant difference at probability of <0.05 was considered for all variables.Of the 761 HIV infected, 64% were females, with a mean age of ± (SD 37.30 (10.4 years. Prevalence of HIV/malaria co-infection was 27.7% with Plasmodium falciparum specie accounting for 99.1%. No statistical significant difference was observed between HIV/malaria co-infection in association to age (p = 0.498 and gender (p = 0.789. A significantly (p = 0.026 higher prevalence (35.2% of co-infection was observed among non-ART patients compared to (26% ART patients. Prevalence of co-infection was significantly lower (20.0% among cotrimoxazole users compared to those not on cotrimoxazole (37

  10. Type 2 Diabetes Mellitus and Increased Risk for Malaria Infection

    This podcast describes research done in Ghana examining a correlation between type 2 diabetes and a possible increased risk for malaria infection in adults. Dr. Manoj Menon, a medical officer in the Division of Parasitic Diseases and Malaria in the Center for Global Health, discusses questions the study raises.

  11. Prevalence of malaria and typhoid co-infections in University of ...

    Mixed infection of malaria caused by Plasmodium species and typhoid fever caused by Salmonella species is often observed in areas where malaria is endemic, and the infection with Salmonella species has been considered by some medical and non-medical personnels to be associated with the malaria parasite infection ...

  12. Non-Genetic Determinants of Mosquito Competence for Malaria Parasites

    Lefèvre, Thierry; Vantaux, Amélie; Dabiré, Kounbobr R.; Mouline, Karine; Cohuet, Anna

    2013-01-01

    Understanding how mosquito vectors and malaria parasites interact is of fundamental interest, and it also offers novel perspectives for disease control. Both the genetic and environmental contexts are known to affect the ability of mosquitoes to support malaria development and transmission, i.e., vector competence. Although the role of environment has long been recognized, much work has focused on host and parasite genetic effects. However, the last few years have seen a surge of studies revealing a great diversity of ways in which non-genetic factors can interfere with mosquito-Plasmodium interactions. Here, we review the current evidence for such environmentally mediated effects, including ambient temperature, mosquito diet, microbial gut flora, and infection history, and we identify additional factors previously overlooked in mosquito-Plasmodium interactions. We also discuss epidemiological implications, and the evolutionary consequences for vector immunity and parasite transmission strategies. Finally, we propose directions for further research and argue that an improved knowledge of non-genetic influences on mosquito-Plasmodium interactions could aid in implementing conventional malaria control measures and contribute to the design of novel strategies. PMID:23818841

  13. Non-genetic determinants of mosquito competence for malaria parasites.

    Thierry Lefèvre

    Full Text Available Understanding how mosquito vectors and malaria parasites interact is of fundamental interest, and it also offers novel perspectives for disease control. Both the genetic and environmental contexts are known to affect the ability of mosquitoes to support malaria development and transmission, i.e., vector competence. Although the role of environment has long been recognized, much work has focused on host and parasite genetic effects. However, the last few years have seen a surge of studies revealing a great diversity of ways in which non-genetic factors can interfere with mosquito-Plasmodium interactions. Here, we review the current evidence for such environmentally mediated effects, including ambient temperature, mosquito diet, microbial gut flora, and infection history, and we identify additional factors previously overlooked in mosquito-Plasmodium interactions. We also discuss epidemiological implications, and the evolutionary consequences for vector immunity and parasite transmission strategies. Finally, we propose directions for further research and argue that an improved knowledge of non-genetic influences on mosquito-Plasmodium interactions could aid in implementing conventional malaria control measures and contribute to the design of novel strategies.

  14. Immunodiagnosis of parasitic infections using nuclear techniques

    1985-07-01

    This report documents the recommendations of the ''Advisory Group on Immunodiagnosis of Parasitic Infections Using Nuclear Techniques'' with a focus on malaria, schistosomiasis and filariasis. Radionuclide tracers are considered an important component of present and future immunological methods for the assessment of the host's humoral and cellular immunity to the parasite and the detection of parasite antigen(s) in human body fluids. The Advisory Group has concluded that there is a continuing need for the development and application of immunodiagnostic methods in parasitic diseases. This report concerns methods which are currently or potentially applicable to immunodiagnostic investigations in parasitic diseases. Reference is made, where appropriate, to recent developments in research which may lead to improvement and standardization of methods now available and the development of new methodology. Separate abstracts on various papers presented were prepared

  15. History of the discovery of the malaria parasites and their vectors

    Cox Francis EG

    2010-02-01

    Full Text Available Abstract Malaria is caused by infection with protozoan parasites belonging to the genus Plasmodium transmitted by female Anopheles species mosquitoes. Our understanding of the malaria parasites begins in 1880 with the discovery of the parasites in the blood of malaria patients by Alphonse Laveran. The sexual stages in the blood were discovered by William MacCallum in birds infected with a related haematozoan, Haemoproteus columbae, in 1897 and the whole of the transmission cycle in culicine mosquitoes and birds infected with Plasmodium relictum was elucidated by Ronald Ross in 1897. In 1898 the Italian malariologists, Giovanni Battista Grassi, Amico Bignami, Giuseppe Bastianelli, Angelo Celli, Camillo Golgi and Ettore Marchiafava demonstrated conclusively that human malaria was also transmitted by mosquitoes, in this case anophelines. The discovery that malaria parasites developed in the liver before entering the blood stream was made by Henry Shortt and Cyril Garnham in 1948 and the final stage in the life cycle, the presence of dormant stages in the liver, was conclusively demonstrated in 1982 by Wojciech Krotoski. This article traces the main events and stresses the importance of comparative studies in that, apart from the initial discovery of parasites in the blood, every subsequent discovery has been based on studies on non-human malaria parasites and related organisms.

  16. Differential attractiveness of humans to the African malaria vector Anopheles gambiae Giles : effects of host characteristics and parasite infection

    Mukabana, W.R.

    2002-01-01

    The results of a series of studies designed to understand the principal factors that determine the differential attractiveness of humans to the malaria vector Anopheles

  17. Estimating sequestered parasite population dynamics in cerebral malaria

    Gravenor, M. B.; van Hensbroek, M. B.; Kwiatkowski, D.

    1998-01-01

    Clinical investigation of malaria is hampered by the lack of a method for estimating the number of parasites that are sequestered in the tissues, for it is these parasites that are thought to be crucial to the pathogenesis of life-threatening complications such as cerebral malaria. We present a

  18. Current status of malaria parasite among blood donors in Port ...

    This study was carried out to determine the prevalence of malaria parasite among blood donors at the Police Clinic Port Harcourt, Rivers State, Nigeria. The standard parasitological techniques using both thick and thin blood films from the donors for the detection of malaria parasite was followed. Venous blood was ...

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

    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

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

    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.

  1. Transformation of the rodent malaria parasite Plasmodium chabaudi

    Spence, Philip J; Cunningham, Deirdre; Jarra, William; Lawton, Jennifer; Langhorne, Jean; Thompson, Joanne

    2011-01-01

    The rodent malaria parasite Plasmodium chabaudi chabaudi shares many features with human malaria species, including P. falciparum, and is the in vivo model of choice for many aspects of malaria research in the mammalian host, from sequestration of parasitized erythrocytes, to antigenic variation and host immunity and immunopathology. this protocol describes an optimized method for the transformation of mature blood-stage P.c. chabaudi and a description of a vector that targets efficient, sing...

  2. Stress Response and Artemisinin Resistance in Malaria Parasite

    2017-07-01

    AWARD NUMBER: W81XWH-16-1-0241 TITLE: Stress Response and Artemisinin Resistance in Malaria Parasite PRINCIPAL INVESTIGATOR: Juan C. Pizarro...SUBTITLE Stress Response and Artemisinin Resistance in Malaria Parasite 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1-0241 5c. PROGRAM ELEMENT...13. SUPPLEMENTARY NOTES 14. ABSTRACT In malaria , drug resistance is a major treat to disease control efforts. Unfortunately, there is a significant

  3. Origin of the human malaria parasite Plasmodium falciparum in gorillas.

    Liu, Weimin; Li, Yingying; Learn, Gerald H; Rudicell, Rebecca S; Robertson, Joel D; Keele, Brandon F; Ndjango, Jean-Bosco N; Sanz, Crickette M; Morgan, David B; Locatelli, Sabrina; Gonder, Mary K; Kranzusch, Philip J; Walsh, Peter D; Delaporte, Eric; Mpoudi-Ngole, Eitel; Georgiev, Alexander V; Muller, Martin N; Shaw, George M; Peeters, Martine; Sharp, Paul M; Rayner, Julian C; Hahn, Beatrice H

    2010-09-23

    Plasmodium falciparum is the most prevalent and lethal of the malaria parasites infecting humans, yet the origin and evolutionary history of this important pathogen remain controversial. Here we develop a single-genome amplification strategy to identify and characterize Plasmodium spp. DNA sequences in faecal samples from wild-living apes. Among nearly 3,000 specimens collected from field sites throughout central Africa, we found Plasmodium infection in chimpanzees (Pan troglodytes) and western gorillas (Gorilla gorilla), but not in eastern gorillas (Gorilla beringei) or bonobos (Pan paniscus). Ape plasmodial infections were highly prevalent, widely distributed and almost always made up of mixed parasite species. Analysis of more than 1,100 mitochondrial, apicoplast and nuclear gene sequences from chimpanzees and gorillas revealed that 99% grouped within one of six host-specific lineages representing distinct Plasmodium species within the subgenus Laverania. One of these from western gorillas comprised parasites that were nearly identical to P. falciparum. In phylogenetic analyses of full-length mitochondrial sequences, human P. falciparum formed a monophyletic lineage within the gorilla parasite radiation. These findings indicate that P. falciparum is of gorilla origin and not of chimpanzee, bonobo or ancient human origin.

  4. Controlled Human Malaria Infection: Applications, Advances, and Challenges.

    Stanisic, Danielle I; McCarthy, James S; Good, Michael F

    2018-01-01

    Controlled human malaria infection (CHMI) entails deliberate infection with malaria parasites either by mosquito bite or by direct injection of sporozoites or parasitized erythrocytes. When required, the resulting blood-stage infection is curtailed by the administration of antimalarial drugs. Inducing a malaria infection via inoculation with infected blood was first used as a treatment (malariotherapy) for neurosyphilis in Europe and the United States in the early 1900s. More recently, CHMI has been applied to the fields of malaria vaccine and drug development, where it is used to evaluate products in well-controlled early-phase proof-of-concept clinical studies, thus facilitating progression of only the most promising candidates for further evaluation in areas where malaria is endemic. Controlled infections have also been used to immunize against malaria infection. Historically, CHMI studies have been restricted by the need for access to insectaries housing infected mosquitoes or suitable malaria-infected individuals. Evaluation of vaccine and drug candidates has been constrained in these studies by the availability of a limited number of Plasmodium falciparum isolates. Recent advances have included cryopreservation of sporozoites, the manufacture of well-characterized and genetically distinct cultured malaria cell banks for blood-stage infection, and the availability of Plasmodium vivax -specific reagents. These advances will help to accelerate malaria vaccine and drug development by making the reagents for CHMI more widely accessible and also enabling a more rigorous evaluation with multiple parasite strains and species. Here we discuss the different applications of CHMI, recent advances in the use of CHMI, and ongoing challenges for consideration. Copyright © 2017 American Society for Microbiology.

  5. Plant Hormone Salicylic Acid Produced by a Malaria Parasite Controls Host Immunity and Cerebral Malaria Outcome.

    Ryuma Matsubara

    Full Text Available The apicomplexan parasite Toxoplasma gondii produces the plant hormone abscisic acid, but it is unclear if phytohormones are produced by the malaria parasite Plasmodium spp., the most important parasite of this phylum. Here, we report detection of salicylic acid, an immune-related phytohormone of land plants, in P. berghei ANKA and T. gondii cell lysates. However, addition of salicylic acid to P. falciparum and T. gondii culture had no effect. We transfected P. falciparum 3D7 with the nahG gene, which encodes a salicylic acid-degrading enzyme isolated from plant-infecting Pseudomonas sp., and established a salicylic acid-deficient mutant. The mutant had a significantly decreased concentration of parasite-synthesized prostaglandin E2, which potentially modulates host immunity as an adaptive evolution of Plasmodium spp. To investigate the function of salicylic acid and prostaglandin E2 on host immunity, we established P. berghei ANKA mutants expressing nahG. C57BL/6 mice infected with nahG transfectants developed enhanced cerebral malaria, as assessed by Evans blue leakage and brain histological observation. The nahG-transfectant also significantly increased the mortality rate of mice. Prostaglandin E2 reduced the brain symptoms by induction of T helper-2 cytokines. As expected, T helper-1 cytokines including interferon-γ and interleukin-2 were significantly elevated by infection with the nahG transfectant. Thus, salicylic acid of Plasmodium spp. may be a new pathogenic factor of this threatening parasite and may modulate immune function via parasite-produced prostaglandin E2.

  6. Motility precedes egress of malaria parasites from oocysts

    Klug, Dennis; Frischknecht, Friedrich

    2017-01-01

    Malaria is transmitted when an infected Anopheles mosquito deposits Plasmodium sporozoites in the skin during a bite. Sporozoites are formed within oocysts at the mosquito midgut wall and are released into the hemolymph, from where they invade the salivary glands and are subsequently transmitted to the vertebrate host. We found that a thrombospondin-repeat containing sporozoite-specific protein named thrombospondin-releated protein 1 (TRP1) is important for oocyst egress and salivary gland invasion, and hence for the transmission of malaria. We imaged the release of sporozoites from oocysts in situ, which was preceded by active motility. Parasites lacking TRP1 failed to migrate within oocysts and did not egress, suggesting that TRP1 is a vital component of the events that precede intra-oocyst motility and subsequently sporozoite egress and salivary gland invasion. DOI: http://dx.doi.org/10.7554/eLife.19157.001 PMID:28115054

  7. The conserved clag multigene family of malaria parasites: essential roles in host-pathogen interaction.

    Gupta, Ankit; Thiruvengadam, Girija; Desai, Sanjay A

    2015-01-01

    The clag multigene family is strictly conserved in malaria parasites, but absent from neighboring genera of protozoan parasites. Early research pointed to roles in merozoite invasion and infected cell cytoadherence, but more recent studies have implicated channel-mediated uptake of ions and nutrients from host plasma. Here, we review the current understanding of this gene family, which appears to be central to host-parasite interactions and an important therapeutic target. Published by Elsevier Ltd.

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

    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.

  9. The impact of HIV-1 on the malaria parasite biomass in adults in sub-Saharan Africa contributes to the emergence of antimalarial drug resistance

    J.P. van Geertruyden (Jean Pierre); J. Menten (Joris); R. Colebunders (Robert); E.L. Korenromp (Eline); U. D'Alessandro (Umberto)

    2008-01-01

    textabstractBackground. HIV-related immune-suppression increases the risk of malaria (infection, disease and treatment failure) and probably the circulating parasite biomass, favoring the emergence of drug resistance parasites. Methods. The additional malaria parasite biomass related to HIV-1

  10. Within-host competition does not select for virulence in malaria parasites; studies with Plasmodium yoelii.

    Hussein M Abkallo

    2015-02-01

    Full Text Available In endemic areas with high transmission intensities, malaria infections are very often composed of multiple genetically distinct strains of malaria parasites. It has been hypothesised that this leads to intra-host competition, in which parasite strains compete for resources such as space and nutrients. This competition may have repercussions for the host, the parasite, and the vector in terms of disease severity, vector fitness, and parasite transmission potential and fitness. It has also been argued that within-host competition could lead to selection for more virulent parasites. Here we use the rodent malaria parasite Plasmodium yoelii to assess the consequences of mixed strain infections on disease severity and parasite fitness. Three isogenic strains with dramatically different growth rates (and hence virulence were maintained in mice in single infections or in mixed strain infections with a genetically distinct strain. We compared the virulence (defined as harm to the mammalian host of mixed strain infections with that of single infections, and assessed whether competition impacted on parasite fitness, assessed by transmission potential. We found that mixed infections were associated with a higher degree of disease severity and a prolonged infection time. In the mixed infections, the strain with the slower growth rate was often responsible for the competitive exclusion of the faster growing strain, presumably through host immune-mediated mechanisms. Importantly, and in contrast to previous work conducted with Plasmodium chabaudi, we found no correlation between parasite virulence and transmission potential to mosquitoes, suggesting that within-host competition would not drive the evolution of parasite virulence in P. yoelii.

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

    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.

  12. The effect of parasitic co-infections on immune responses in Gabon : particular emphasis on malaria and helminths

    Ateba, Ngoa U.

    2016-01-01

    The work presented in this thesis aimed at increasing our understanding of the effect of helminths on Plasmodium spp. immune response in co-infected individuals living in endemic countries. It presents data from studies conducted in rural and semi urban areas of Lambaréné (Gabon) where the burden of

  13. Parasite Infection, Carcinogenesis and Human Malignancy.

    van Tong, Hoang; Brindley, Paul J; Meyer, Christian G; Velavan, Thirumalaisamy P

    2017-02-01

    Cancer may be induced by many environmental and physiological conditions. Infections with viruses, bacteria and parasites have been recognized for years to be associated with human carcinogenicity. Here we review current concepts of carcinogenicity and its associations with parasitic infections. The helminth diseases schistosomiasis, opisthorchiasis, and clonorchiasis are highly carcinogenic while the protozoan Trypanosoma cruzi, the causing agent of Chagas disease, has a dual role in the development of cancer, including both carcinogenic and anticancer properties. Although malaria per se does not appear to be causative in carcinogenesis, it is strongly associated with the occurrence of endemic Burkitt lymphoma in areas holoendemic for malaria. The initiation of Plasmodium falciparum related endemic Burkitt lymphoma requires additional transforming events induced by the Epstein-Barr virus. Observations suggest that Strongyloides stercoralis may be a relevant co-factor in HTLV-1-related T cell lymphomas. This review provides an overview of the mechanisms of parasitic infection-induced carcinogenicity. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Dual fluorescence labeling of surface-exposed and internal proteins in erythrocytes infected with the malaria parasite Plasmodium falciparum

    Bengtsson, Dominique C; Sowa, Kordai M P; Arnot, David E

    2008-01-01

    There is a need for improved methods for in situ localization of surface proteins on Plasmodium falciparum-infected erythrocytes to help understand how these antigens are trafficked to, and positioned within, the host cell membrane. This protocol for confocal immunofluorescence microscopy combines...... and permeabilization; indirect labeling of the internal antigen using a secondary antibody tagged with a spectrally distinct fluorescent dye; and detection of the differentially labeled antigens using a laser scanning confocal microscope. The protocol can be completed in approximately 7 h. Although the protocol...... surface antigen labeling on live cells with subsequent fixation and permeabilization, which enables antibodies to penetrate the cell and label internal antigens. The key steps of the protocol are as follows: indirect labeling of the surface antigen using a fluorescently tagged secondary antibody; fixation...

  15. Immunity to parasitic infection

    Lamb, Tracey J

    2012-01-01

    .... Often endemic in developing countries many parasitic diseases are neglected in terms of research funding and much remains to be understood about parasites and the interactions they have with the immune system...

  16. Erythropoiesis in Malaria Infections and Factors Modifying the Erythropoietic Response

    Vrushali A. Pathak

    2016-01-01

    Full Text Available Anemia is the primary clinical manifestation of malarial infections and is responsible for the substantial rate of morbidity. The pathophysiology discussed till now catalogued several causes for malarial anemia among which ineffective erythropoiesis being remarkable one occurs silently in the bone marrow. A systematic literature search was performed and summarized information on erythropoietic response upon malaria infection and the factors responsible for the same. This review summarizes the clinical and experimental studies on patients, mouse models, and in vitro cell cultures reporting erythropoietic changes upon malaria infection as well as factors accountable for the same. Inadequate erythropoietic response during malaria infection may be the collective effect of various mediators generated by host immune response as well as parasite metabolites. The interplay between various modulators causing the pathophysiology needs to be explored further. Globin gene expression profiling upon malaria infection should also be looked into as abnormal production of globin chains could be a possible contributor to ineffective erythropoiesis.

  17. Non-Genetic Determinants of Mosquito Competence for Malaria Parasites

    Lef?vre, Thierry; Vantaux, Am?lie; Dabir?, Kounbobr R.; Mouline, Karine; Cohuet, Anna

    2013-01-01

    Understanding how mosquito vectors and malaria parasites interact is of fundamental interest, and it also offers novel perspectives for disease control. Both the genetic and environmental contexts are known to affect the ability of mosquitoes to support malaria development and transmission, i.e., vector competence. Although the role of environment has long been recognized, much work has focused on host and parasite genetic effects. However, the last few years have seen a surge of studies reve...

  18. Environmental Constraints Guide Migration of Malaria Parasites during Transmission

    Hellmann, Janina Kristin; Münter, Sylvia; Kudryashev, Mikhail; Schulz, Simon; Heiss, Kirsten; Müller, Ann-Kristin; Matuschewski, Kai; Spatz, Joachim P.; Schwarz, Ulrich S.; Frischknecht, Friedrich

    2011-01-01

    Migrating cells are guided in complex environments mainly by chemotaxis or structural cues presented by the surrounding tissue. During transmission of malaria, parasite motility in the skin is important for Plasmodium sporozoites to reach the blood circulation. Here we show that sporozoite migration varies in different skin environments the parasite encounters at the arbitrary sites of the mosquito bite. In order to systematically examine how sporozoite migration depends on the structure of the environment, we studied it in micro-fabricated obstacle arrays. The trajectories observed in vivo and in vitro closely resemble each other suggesting that structural constraints can be sufficient to guide Plasmodium sporozoites in complex environments. Sporozoite speed in different environments is optimized for migration and correlates with persistence length and dispersal. However, this correlation breaks down in mutant sporozoites that show adhesion impairment due to the lack of TRAP-like protein (TLP) on their surfaces. This may explain their delay in infecting the host. The flexibility of sporozoite adaption to different environments and a favorable speed for optimal dispersal ensures efficient host switching during malaria transmission. PMID:21698220

  19. Evaluation of concurrent malaria and dengue infections among febrile patients

    Parul D Shah

    2017-01-01

    Full Text Available Context: Despite a wide overlap between endemic areas for two important vector-borne infections, malaria and dengue, published reports of co-infections are scarce till date. Aims: To find the incidence of dengue and malaria co-infection as well as to ascertain the severity of such dengue and malaria co-infection based on clinical and haematological parameters. Setting and Design: Observational, retrospective cross-sectional study was designed including patients who consulted the tertiary care hospital of Ahmedabad seeking treatment for fever compatible with malaria and/or dengue. Subjects and Methods: A total of 8364 serum samples from clinically suspected cases of fever compatible with malaria and/or dengue were collected. All samples were tested for dengue NS-1 antigen before 5 days of onset of illness and for dengue IgM after 5 days of onset of illness. In all samples, malaria diagnosis was based on the identification of Plasmodium parasites on a thin and thick blood films microscopy. Results: Only 10.27% (859 patients with fever were tested positive for dengue and 5.1% (434 were tested positive for malaria. 3.14% (27 dengue cases show concurrent infection with malarial parasites. Hepatomegaly and jaundice 37.03% (10, haemorrhagic manifestations 18.51% (5 and kidney failure 3.7% (1, haemoglobin <12 g/dl 100% (27 and thrombocytopenia (platelet count <150,000/cmm 96.29% (26 were common in malaria and dengue co-infections and were much more common in Plasmodium falciparum infections. Conclusion: All febrile patients must be tested for malaria and dengue, both otherwise one of them will be missed in case of concurrent infections which could lead to severe diseases with complications.

  20. Malaria and helminth co-infections in school and preschool children

    Kinung'hi, Safari M; Magnussen, Pascal; Kaatano, Godfrey M

    2014-01-01

    Malaria, schistosomiasis and soil transmitted helminth infections (STH) are important parasitic infections in Sub-Saharan Africa where a significant proportion of people are exposed to co-infections of more than one parasite. In Tanzania, these infections are a major public health problem particu...

  1. Type 2 Diabetes Mellitus and Increased Risk for Malaria Infection

    2010-09-23

    This podcast describes research done in Ghana examining a correlation between type 2 diabetes and a possible increased risk for malaria infection in adults. Dr. Manoj Menon, a medical officer in the Division of Parasitic Diseases and Malaria in the Center for Global Health, discusses questions the study raises.  Created: 9/23/2010 by National Center for Emerging and Zoonotic Infectious Diseases; Center for Global Health.   Date Released: 9/23/2010.

  2. Malaria parasite carriage and risk determinants in a rural population: a malariometric survey in Rwanda.

    Kateera, Fredrick; Mens, Petra F; Hakizimana, Emmanuel; Ingabire, Chantal M; Muragijemariya, Liberata; Karinda, Parfait; Grobusch, Martin P; Mutesa, Leon; van Vugt, Michèle

    2015-01-21

    Based on routine health facility case data, Rwanda has achieved a significant malaria burden reduction in the past ten years. However, community-based malaria parasitaemia burden and reasons for continued residual infections, despite a high coverage of control interventions, have yet to be characterized. Measurement of malaria parasitaemia rates and evaluation of associated risk factors among asymptomatic household members in a rural community in Rwanda were conducted. A malariometric household survey was conducted between June and November 2013, involving 12,965 persons living in 3,989 households located in 35 villages in a sector in eastern Rwanda. Screening for malaria parasite carriage and collection of demographic, socio-economic, house structural features, and prior fever management data, were performed. Logistic regression models with adjustment for within- and between-households clustering were used to assess malaria parasitaemia risk determinants. Overall, malaria parasitaemia was found in 652 (5%) individuals, with 518 (13%) of households having at least one parasitaemic member. High malaria parasite carriage risk was associated with being male, child or adolescent (age group 4-15), reported history of fever and living in a household with multiple occupants. A malaria parasite carriage risk-protective effect was associated with living in households of, higher socio-economic status, where the head of household was educated and where the house floor or walls were made of cement/bricks rather than mud/earth/wood materials. Parasitaemia cases were found to significantly cluster in the Gikundamvura area that neighbours marshlands. Overall, Ruhuha Sector can be classified as hypo-endemic, albeit with a particular 'cell of villages' posing a higher risk for malaria parasitaemia than others. Efforts to further reduce transmission and eventually eliminate malaria locally should focus on investments in programmes that improve house structure features (that limit

  3. Enhanced transmission of drug-resistant parasites to mosquitoes following drug treatment in rodent malaria.

    Andrew S Bell

    Full Text Available The evolution of drug resistant Plasmodium parasites is a major challenge to effective malaria control. In theory, competitive interactions between sensitive parasites and resistant parasites within infections are a major determinant of the rate at which parasite evolution undermines drug efficacy. Competitive suppression of resistant parasites in untreated hosts slows the spread of resistance; competitive release following treatment enhances it. Here we report that for the murine model Plasmodium chabaudi, co-infection with drug-sensitive parasites can prevent the transmission of initially rare resistant parasites to mosquitoes. Removal of drug-sensitive parasites following chemotherapy enabled resistant parasites to transmit to mosquitoes as successfully as sensitive parasites in the absence of treatment. We also show that the genetic composition of gametocyte populations in host venous blood accurately reflects the genetic composition of gametocytes taken up by mosquitoes. Our data demonstrate that, at least for this mouse model, aggressive chemotherapy leads to very effective transmission of highly resistant parasites that are present in an infection, the very parasites which undermine the long term efficacy of front-line drugs.

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

    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

  5. A review of mixed malaria species infections in anopheline mosquitoes

    Day Nicholas PJ

    2011-08-01

    Full Text Available Abstract Background In patients with malaria mixed species infections are common and under reported. In PCR studies conducted in Asia mixed infection rates often exceed 20%. In South-East Asia, approximately one third of patients treated for falciparum malaria experience a subsequent Plasmodium vivax infection with a time interval suggesting relapse. It is uncertain whether the two infections are acquired simultaneously or separately. To determine whether mixed species infections in humans are derived from mainly from simultaneous or separate mosquito inoculations the literature on malaria species infection in wild captured anopheline mosquitoes was reviewed. Methods The biomedical literature was searched for studies of malaria infection and species identification in trapped wild mosquitoes and artificially infected mosquitoes. The study location and year, collection methods, mosquito species, number of specimens, parasite stage examined (oocysts or sporozoites, and the methods of parasite detection and speciation were tabulated. The entomological results in South East Asia were compared with mixed infection rates documented in patients in clinical studies. Results In total 63 studies were identified. Individual anopheline mosquitoes were examined for different malaria species in 28 of these. There were 14 studies from Africa; four with species evaluations in individual captured mosquitoes (SEICM. One study, from Ghana, identified a single mixed infection. No mixed infections were identified in Central and South America (seven studies, two SEICM. 42 studies were conducted in Asia and Oceania (11 from Thailand; 27 SEICM. The proportion of anophelines infected with Plasmodium falciparum parasites only was 0.51% (95% CI: 0.44 to 0.57%, for P. vivax only was 0.26% (95% CI: 0.21 to 0.30%, and for mixed P. falciparum and P. vivax infections was 0.036% (95% CI: 0.016 to 0.056%. The proportion of mixed infections in mosquitoes was significantly higher

  6. Interferon-Mediated Innate Immune Responses against Malaria Parasite Liver Stages

    Jessica L. Miller

    2014-04-01

    Full Text Available Mosquito-transmitted malaria parasites infect hepatocytes and asymptomatically replicate as liver stages. Using RNA sequencing, we show that a rodent malaria liver-stage infection stimulates a robust innate immune response including type I interferon (IFN and IFNγ pathways. Liver-stage infection is suppressed by these infection-engendered innate responses. This suppression was abrogated in mice deficient in IFNγ, the type I IFN α/β receptor (IFNAR, and interferon regulatory factor 3. Natural killer and CD49b+CD3+ natural killer T (NKT cells increased in the liver after a primary infection, and CD1d-restricted NKT cells, which secrete IFNγ, were critical in reducing liver-stage burden of a secondary infection. Lack of IFNAR signaling abrogated the increase in NKT cell numbers in the liver, showing a link between type I IFN signaling, cell recruitment, and subsequent parasite elimination. Our findings demonstrate innate immune sensing of malaria parasite liver-stage infection and that the ensuing innate responses can eliminate the parasite.

  7. Compartmentation of redox metabolism in malaria parasites.

    Sebastian Kehr

    Full Text Available Malaria, caused by the apicomplexan parasite Plasmodium, still represents a major threat to human health and welfare and leads to about one million human deaths annually. Plasmodium is a rapidly multiplying unicellular organism undergoing a complex developmental cycle in man and mosquito - a life style that requires rapid adaptation to various environments. In order to deal with high fluxes of reactive oxygen species and maintain redox regulatory processes and pathogenicity, Plasmodium depends upon an adequate redox balance. By systematically studying the subcellular localization of the major antioxidant and redox regulatory proteins, we obtained the first complete map of redox compartmentation in Plasmodium falciparum. We demonstrate the targeting of two plasmodial peroxiredoxins and a putative glyoxalase system to the apicoplast, a non-photosynthetic plastid. We furthermore obtained a complete picture of the compartmentation of thioredoxin- and glutaredoxin-like proteins. Notably, for the two major antioxidant redox-enzymes--glutathione reductase and thioredoxin reductase--Plasmodium makes use of alternative-translation-initiation (ATI to achieve differential targeting. Dual localization of proteins effected by ATI is likely to occur also in other Apicomplexa and might open new avenues for therapeutic intervention.

  8. The Effect of Indoor Residual Spraying on the Prevalence of Malaria Parasite Infection, Clinical Malaria and Anemia in an Area of Perennial Transmission and Moderate Coverage of Insecticide Treated Nets in Western Kenya.

    John E Gimnig

    Full Text Available Insecticide treated nets (ITNs and indoor residual spraying (IRS have been scaled up for malaria prevention in sub-Saharan Africa. However, there are few studies on the benefit of implementing IRS in areas with moderate to high coverage of ITNs. We evaluated the impact of an IRS program on malaria related outcomes in western Kenya, an area of intense perennial malaria transmission and moderate ITN coverage (55-65% use of any net the previous night.The Kenya Division of Malaria Control, with support from the US President's Malaria Initiative, conducted IRS in one lowland endemic district with moderate coverage of ITNs. Surveys were conducted in the IRS district and a neighboring district before IRS, after one round of IRS in July-Sept 2008 and after a second round of IRS in April-May 2009. IRS was conducted with pyrethroid insecticides. At each survey, 30 clusters were selected for sampling and within each cluster, 12 compounds were randomly selected. The primary outcomes measured in all residents of selected compounds included malaria parasitemia, clinical malaria (P. falciparum infection plus history of fever and anemia (Hb<8 of all residents in randomly selected compounds. At each survey round, individuals from the IRS district were matched to those from the non-IRS district using propensity scores and multivariate logistic regression models were constructed based on the matched dataset.At baseline and after one round of IRS, there were no differences between the two districts in the prevalence of malaria parasitemia, clinical malaria or anemia. After two rounds of IRS, the prevalence of malaria parasitemia was 6.4% in the IRS district compared to 16.7% in the comparison district (OR = 0.36, 95% CI = 0.22-0.59, p<0.001. The prevalence of clinical malaria was also lower in the IRS district (1.8% vs. 4.9%, OR = 0.37, 95% CI = 0.20-0.68, p = 0.001. The prevalence of anemia was lower in the IRS district but only in children under 5 years of age (2

  9. Mitosis in the Human Malaria Parasite Plasmodium falciparum ▿

    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 contri...

  10. An Unusual Prohibitin Regulates Malaria Parasite Mitochondrial Membrane Potential

    Joachim Michael Matz

    2018-04-01

    Full Text Available Summary: Proteins of the stomatin/prohibitin/flotillin/HfIK/C (SPFH family are membrane-anchored and perform diverse cellular functions in different organelles. Here, we investigate the SPFH proteins of the murine malaria model parasite Plasmodium berghei, the conserved prohibitin 1, prohibitin 2, and stomatin-like protein and an unusual prohibitin-like protein (PHBL. The SPFH proteins localize to the parasite mitochondrion. While the conserved family members could not be deleted from the Plasmodium genome, PHBL was successfully ablated, resulting in impaired parasite fitness and attenuated virulence in the mammalian host. Strikingly, PHBL-deficient parasites fail to colonize the Anopheles vector because of complete arrest during ookinete development in vivo. We show that this arrest correlates with depolarization of the mitochondrial membrane potential (ΔΨmt. Our results underline the importance of SPFH proteins in the regulation of core mitochondrial functions and suggest that fine-tuning of ΔΨmt in malarial parasites is critical for colonization of the definitive host. : Matz et al. present an experimental genetics study of an unusual prohibitin-like protein in the malaria parasite and find that it regulates mitochondrial membrane polarity. Ablation of this protein causes almost complete mitochondrial depolarization in the mosquito vector, which, in turn, leads to a block in malaria parasite transmission. Keywords: Plasmodium berghei, malaria, SPFH, prohibitin, stomatin-like protein, mitochondrion, membrane potential, ookinete, transmission

  11. Prevalence of malaria infection in children in Anambra state, Nigeria ...

    This study was carried out to estimate the effects of this new WHO policy on the prevalence of malaria parasite infection in children from selected communities in Anambra State, Nigeria. This study was conducted in thirteen communities purposively selected from thirteen local government areas in Anambra State using ...

  12. Malaria

    ... bites you, the parasite can get into your blood. The parasite lays eggs, which develop into more parasites. They ... cells until you get very sick. Because the parasites live in the blood, malaria can also be spread through other ways. ...

  13. Fall in hematocrit per 1000 parasites cleared from peripheral blood: a simple method for estimating drug-related fall in hematocrit after treatment of malaria infections.

    Gbotosho, Grace Olusola; Okuboyejo, Titilope; Happi, Christian Tientcha; Sowunmi, Akintunde

    2014-01-01

    A simple method to estimate antimalarial drug-related fall in hematocrit (FIH) after treatment of Plasmodium falciparum infections in the field is described. The method involves numeric estimation of the relative difference in hematocrit at baseline (pretreatment) and the first 1 or 2 days after treatment begun as numerator and the corresponding relative difference in parasitemia as the denominator, and expressing it per 1000 parasites cleared from peripheral blood. Using the method showed that FIH/1000 parasites cleared from peripheral blood (cpb) at 24 or 48 hours were similar in artemether-lumefantrine and artesunate-amodiaquine-treated children (0.09; 95% confidence interval, 0.052-0.138 vs 0.10; 95% confidence interval, 0.069-0.139%; P = 0.75) FIH/1000 parasites cpb in patients with higher parasitemias were significantly (P 1000 parasites cpb were similar in anemic and nonanemic children. Estimation of FIH/1000 parasites cpb is simple, allows estimation of relatively conserved hematocrit during treatment, and can be used in both observational studies and clinical trials involving antimalarial drugs.

  14. Primary peak and chronic malaria infection levels are correlated in experimentally infected great reed warblers.

    Asghar, Muhammad; Westerdahl, Helena; Zehtindjiev, Pavel; Ilieva, Mihaela; Hasselquist, Dennis; Bensch, Staffan

    2012-09-01

    Malaria parasites often manage to maintain an infection for several months or years in their vertebrate hosts. In humans, rodents and birds, most of the fitness costs associated with malaria infections are in the short initial primary (high parasitaemia) phase of the infection, whereas the chronic phase (low parasitaemia) is more benign to the host. In wild birds, malaria parasites have mainly been studied during the chronic phase of the infection. This is because the initial primary phase of infection is short in duration and infected birds with severe disease symptoms tend to hide in sheltered places and are thus rarely caught and sampled. We therefore wanted to investigate the relationship between the parasitaemia during the primary and chronic phases of the infection using an experimental infection approach. We found a significant positive correlation between parasitaemia in the primary peak and the subsequent chronic phase of infection when we experimentally infected great reed warblers (Acrocephalus arundinaceus) with Plasmodium ashfordi. The reason for this association remains to be understood, but might arise from individual variation in exoerythrocytic parasite reservoirs in hosts, parasite antigenic diversity and/or host genetics. Our results suggest that the chronic phase parasitaemia can be used to qualitatively infer the parasitaemia of the preceding and more severe primary phase, which is a very important finding for studies of avian malaria in wild populations.

  15. Protocol for production of a genetic cross of the rodent malaria parasites.

    Pattaradilokrat, Sittiporn; Li, Jian; Su, Xin-zhuan

    2011-01-03

    Variation in response to antimalarial drugs and in pathogenicity of malaria parasites is of biologic and medical importance. Linkage mapping has led to successful identification of genes or loci underlying various traits in malaria parasites of rodents and humans. The malaria parasite Plasmodium yoelii is one of many malaria species isolated from wild African rodents and has been adapted to grow in laboratories. This species reproduces many of the biologic characteristics of the human malaria parasites; genetic markers such as microsatellite and amplified fragment length polymorphism (AFLP) markers have also been developed for the parasite. Thus, genetic studies in rodent malaria parasites can be performed to complement research on Plasmodium falciparum. Here, we demonstrate the techniques for producing a genetic cross in P. yoelii that were first pioneered by Drs. David Walliker, Richard Carter, and colleagues at the University of Edinburgh. Genetic crosses in P. yoelii and other rodent malaria parasites are conducted by infecting mice Mus musculus with an inoculum containing gametocytes of two genetically distinct clones that differ in phenotypes of interest and by allowing mosquitoes to feed on the infected mice 4 days after infection. The presence of male and female gametocytes in the mouse blood is microscopically confirmed before feeding. Within 48 hrs after feeding, in the midgut of the mosquito, the haploid gametocytes differentiate into male and female gametes, fertilize, and form a diploid zygote (Fig. 1). During development of a zygote into an ookinete, meiosis appears to occur. If the zygote is derived through cross-fertilization between gametes of the two genetically distinct parasites, genetic exchanges (chromosomal reassortment and cross-overs between the non-sister chromatids of a pair of homologous chromosomes; Fig. 2) may occur, resulting in recombination of genetic material at homologous loci. Each zygote undergoes two successive nuclear

  16. Licochalcone A, a new antimalarial agent, inhibits in vitro growth of the human malaria parasite Plasmodium falciparum and protects mice from P. yoelii infection

    Chen, M; Theander, T G; Christensen, S B

    1994-01-01

    Licochalcone A, isolated from Chinese licorice roots, inhibited the in vitro growth of both chloroquine-susceptible (3D7) and chloroquine-resistant (Dd2) Plasmodium falciparum strains in a [3H]hypoxanthine uptake assay. The growth inhibition of the chloroquine-resistant strain by licochalcone A w...... that licochalcone A exhibits potent antimalarial activity and might be developed into a new antimalarial drug....... A was similar to that of the chloroquine-susceptible strain. To examine the activity of licochalcone A on the different asexual blood stages of the parasite, licochalcone A was added to highly synchronized cultures containing rings, trophozoites, and schizonts. The growth of the parasites at all stages...... was inhibited by licochalcone A. The in vivo activity of licochalcone A was tested in a mouse model of infection with P. yoelii. Licochalcone A administered either intraperitoneally or orally for 3 to 6 days protected the mice from the otherwise lethal P. yoelii infection. These results demonstrate...

  17. Heritability of the human infectious reservoir of malaria parasites.

    Yaye Ramatoulaye Lawaly

    Full Text Available BACKGROUND: Studies on human genetic factors associated with malaria have hitherto concentrated on their role in susceptibility to and protection from disease. In contrast, virtually no attention has been paid to the role of human genetics in eliciting the production of parasite transmission stages, the gametocytes, and thus enhancing the spread of disease. METHODS AND FINDINGS: We analysed four longitudinal family-based cohort studies from Senegal and Thailand followed for 2-8 years and evaluated the relative impact of the human genetic and non-genetic factors on gametocyte production in infections of Plasmodium falciparum or P. vivax. Prevalence and density of gametocyte carriage were evaluated in asymptomatic and symptomatic infections by examination of Giemsa-stained blood smears and/or RT-PCR (for falciparum in one site. A significant human genetic contribution was found to be associated with gametocyte prevalence in asymptomatic P. falciparum infections. By contrast, there was no heritability associated with the production of gametocytes for P. falciparum or P. vivax symptomatic infections. Sickle cell mutation, HbS, was associated with increased gametocyte prevalence but its contribution was small. CONCLUSIONS: The existence of a significant human genetic contribution to gametocyte prevalence in asymptomatic infections suggests that candidate gene and genome wide association approaches may be usefully applied to explore the underlying human genetics. Prospective epidemiological studies will provide an opportunity to generate novel and perhaps more epidemiologically pertinent gametocyte data with which similar analyses can be performed and the role of human genetics in parasite transmission ascertained.

  18. Transmission traits of malaria parasites within the mosquito: Genetic variation, phenotypic plasticity, and consequences for control.

    Lefevre, Thierry; Ohm, Johanna; Dabiré, Kounbobr R; Cohuet, Anna; Choisy, Marc; Thomas, Matthew B; Cator, Lauren

    2018-04-01

    Evaluating the risk of emergence and transmission of vector-borne diseases requires knowledge of the genetic and environmental contributions to pathogen transmission traits. Compared to the significant effort devoted to understanding the biology of malaria transmission from vertebrate hosts to mosquito vectors, the strategies that malaria parasites have evolved to maximize transmission from vectors to vertebrate hosts have been largely overlooked. While determinants of infection success within the mosquito host have recently received attention, the causes of variability for other key transmission traits of malaria, namely the duration of parasite development and its virulence within the vector, as well as its ability to alter mosquito behavior, remain largely unknown. This important gap in our knowledge needs to be bridged in order to obtain an integrative view of the ecology and evolution of malaria transmission strategies. Associations between transmission traits also need to be characterized, as they trade-offs and constraints could have important implications for understanding the evolution of parasite transmission. Finally, theoretical studies are required to evaluate how genetic and environmental influences on parasite transmission traits can shape malaria dynamics and evolution in response to disease control.

  19. Heterologous Infection of Pregnant Mice Induces Low Birth Weight and Modifies Offspring Susceptibility to Malaria.

    Ankur Sharma

    Full Text Available Pregnancy malaria (PM is associated with poor pregnancy outcomes, and can arise due to relapse, recrudescence or a re-infection with heterologous parasites. We have used the Plasmodium chabaudi model of pregnancy malaria in C57BL/6 mice to examine recrudescence and heterologous infection using CB and AS parasite strains. After an initial course of patent parasitemia and first recrudescence, CB but not AS parasites were observed to recrudesce again in most animals that became pregnant. Pregnancy exacerbated heterologous CB infection of AS-experienced mice, leading to mortality and impaired post-natal growth of pups. Parasites were detected in placental blood without evidence of sequestration, unlike P. falciparum but similar to other malaria species that infect pregnant women. Inflammatory cytokine levels were elevated in pregnant females during malaria, and associated with intensity of infection and with poor outcomes. Pups born to dams during heterologous infection were more resistant to malaria infections at 6-7 weeks of age, compared to pups born to malaria-experienced but uninfected dams or to malaria-naïve dams. In summary, our mouse model reproduces several features of human PM, including recrudescences, heterologous infections, poor pregnancy outcomes associated with inflammatory cytokines, and modulation of offspring susceptibility to malaria. This model should be further studied to explore mechanisms underlying PM pathogenesis.

  20. Submicroscopic malaria parasite carriage: how reproducible are polymerase chain reaction-based methods?

    Daniela Camargos Costa

    2014-02-01

    Full Text Available The polymerase chain reaction (PCR-based methods for the diagnosis of malaria infection are expected to accurately identify submicroscopic parasite carriers. Although a significant number of PCR protocols have been described, few studies have addressed the performance of PCR amplification in cases of field samples with submicroscopic malaria infection. Here, the reproducibility of two well-established PCR protocols (nested-PCR and real-time PCR for the Plasmodium 18 small subunit rRNA gene were evaluated in a panel of 34 blood field samples from individuals that are potential reservoirs of malaria infection, but were negative for malaria by optical microscopy. Regardless of the PCR protocol, a large variation between the PCR replicates was observed, leading to alternating positive and negative results in 38% (13 out of 34 of the samples. These findings were quite different from those obtained from the microscopy-positive patients or the unexposed individuals; the diagnosis of these individuals could be confirmed based on the high reproducibility and specificity of the PCR-based protocols. The limitation of PCR amplification was restricted to the field samples with very low levels of parasitaemia because titrations of the DNA templates were able to detect < 3 parasites/µL in the blood. In conclusion, conventional PCR protocols require careful interpretation in cases of submicroscopic malaria infection, as inconsistent and false-negative results can occur.

  1. The malaria parasite Plasmodium relictum in the endemic avifauna of eastern Cuba.

    Soares, Letícia; Marra, Peter; Gray, Lindsey; Ricklefs, Robert E

    2017-12-01

    Island populations are vulnerable to introduced pathogens, as evidenced by extinction or population decline of several endemic Hawaiian birds caused by the malaria parasite, Plasmodium relictum (order Haemosporida). We analyzed blood samples from 363 birds caught near Guantánamo Bay, Cuba, for the presence of haemosporidian infections. We characterized parasite lineages by determining nucleotide variation of the parasite's mitochondrial cyt b gene. Fifty-nine individuals were infected, and we identified 7 lineages of haemosporidian parasites. Fifty individuals were infected by 6 Haemoproteus sp. lineages, including a newly characterized lineage of Haem. (Parahaemoproteus) sp. CUH01. Nine individuals carried the P. relictum lineage GRW4, including 5 endemic Cuban Grassquits (Tiaris canorus) and 1 migratory Cape May Warbler (Setophaga tigrina). A sequence of the merozoite surface protein gene from one Cuban Grassquit infected with GRW4 matched that of the Hawaiian haplotype Pr9. Our results indicate that resident and migratory Cuban birds are infected with a malaria lineage that has severely affected populations of several endemic Hawaiian birds. We suggest GRW4 may be associated with the lack of several bird species on Cuba that are ubiquitous elsewhere in the West Indies. From the standpoint of avian conservation in the Caribbean Basin, it will be important to determine the distribution of haemosporidian parasites, especially P. relictum GRW4, in Cuba as well as the pathogenicity of this lineage in species that occur and are absent from Cuba. © 2017 Society for Conservation Biology.

  2. Nanomimics of host cell membranes block invasion and expose invasive malaria parasites.

    Najer, Adrian; Wu, Dalin; Bieri, Andrej; Brand, Françoise; Palivan, Cornelia G; Beck, Hans-Peter; Meier, Wolfgang

    2014-12-23

    The fight against most infectious diseases, including malaria, is often hampered by the emergence of drug resistance and lack or limited efficacies of vaccines. Therefore, new drugs, vaccines, or other strategies to control these diseases are needed. Here, we present an innovative nanotechnological strategy in which the nanostructure itself represents the active substance with no necessity to release compounds to attain therapeutic effect and which might act in a drug- and vaccine-like dual function. Invasion of Plasmodium falciparum parasites into red blood cells was selected as a biological model for the initial validation of this approach. Stable nanomimics-polymersomes presenting receptors required for parasite attachment to host cells-were designed to efficiently interrupt the life cycle of the parasite by inhibiting invasion. A simple way to build nanomimics without postformation modifications was established. First, a block copolymer of the receptor with a hydrophobic polymer was synthesized and then mixed with a polymersome-forming block copolymer. The resulting nanomimics bound parasite-derived ligands involved in the initial attachment to host cells and they efficiently blocked reinvasion of malaria parasites after their egress from host cells in vitro. They exhibited efficacies of more than 2 orders of magnitude higher than the soluble form of the receptor, which can be explained by multivalent interactions of several receptors on one nanomimic with multiple ligands on the infective parasite. In the future, our strategy might offer interesting treatment options for severe malaria or a way to modulate the immune response.

  3. Insights on Heme Synthesis in the Malaria Parasite.

    Nagaraj, Viswanathan A; Padmanaban, Govindarajan

    2017-08-01

    The malaria parasite has a functional heme-biosynthetic pathway, although it can access host hemoglobin-heme. The heme pathway is dispensable for blood stages, but essential in the mosquito stages which do not acquire hemoglobin-heme. We propose that the blood stage parasites maintain a dynamic heme pool through multiple back-up mechanisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Changes in lipid composition during sexual development of the malaria parasite Plasmodium falciparum.

    Tran, Phuong N; Brown, Simon H J; Rug, Melanie; Ridgway, Melanie C; Mitchell, Todd W; Maier, Alexander G

    2016-02-06

    The development of differentiated sexual stages (gametocytes) within human red blood cells is essential for the propagation of the malaria parasite, since only mature gametocytes will survive in the mosquito's midgut. Hence gametocytogenesis is a pre-requisite for transmission of the disease. Physiological changes involved in sexual differentiation are still enigmatic. In particular the lipid metabolism-despite being central to cellular regulation and development-is not well explored. Here the lipid profiles of red blood cells infected with the five different sexual stages of Plasmodium falciparum were analysed by mass spectrometry and compared to those from uninfected and asexual trophozoite infected erythrocytes. Fundamental differences between erythrocytes infected with the different parasite stages were revealed. In mature gametocytes many lipids that decrease in the trophozoite and early gametocyte infected red blood cells are regained. In particular, regulators of membrane fluidity, cholesterol and sphingomyelin, increased significantly during gametocyte maturation. Neutral lipids (serving mainly as caloriometric reserves) increased from 3 % of total lipids in uninfected to 27 % in stage V gametocyte infected red blood cells. The major membrane lipid class (phospholipids) decreased during gametocyte development. The lipid profiles of infected erythrocytes are characteristic for the particular parasite life cycle and maturity stages of gametocytes. The obtained lipid profiles are crucial in revealing the lipid metabolism of malaria parasites and identifying targets to interfere with this deadly disease.

  5. Examining the Reticulocyte Preference of Two Plasmodium berghei Strains during Blood-Stage Malaria Infection

    Neha Thakre

    2018-02-01

    Full Text Available The blood-stage of the Plasmodium parasite is one of the key phases within its life cycle that influences disease progression during a malaria infection. The efficiency of the parasite in infecting red blood cells (RBC determines parasite load and parasite-induced hemolysis that is responsible for the development of anemia and potentially drives severe disease progression. However, the molecular factors defining the infectivity of Plasmodium parasites have not been completely identified so far. Using the Plasmodium berghei mouse model for malaria, we characterized and compared the blood-stage infection dynamics of PbANKA WT and a mutant parasite strain lacking a novel Plasmodium antigen, PbmaLS_05, that is well conserved in both human and animal Plasmodium parasite strains. Infection of mice with parasites lacking PbmaLS_05 leads to lower parasitemia levels and less severe disease progression in contrast to mice infected with the wildtype PbANKA strain. To specifically determine the effect of deleting PbmaLS_05 on parasite infectivity we developed a mathematical model describing erythropoiesis and malarial infection of RBC. By applying our model to experimental data studying infection dynamics under normal and drug-induced altered erythropoietic conditions, we found that both PbANKA and PbmaLS_05 (- parasite strains differed in their infectivity potential during the early intra-erythrocytic stage of infection. Parasites lacking PbmaLS_05 showed a decreased ability to infect RBC, and immature reticulocytes in particular that are usually a preferential target of the parasite. These altered infectivity characteristics limit parasite burden and affect disease progression. Our integrative analysis combining mathematical models and experimental data suggests that deletion of PbmaLS_05 affects productive infection of reticulocytes, which makes this antigen a useful target to analyze the actual processes relating RBC preferences to the development of

  6. Droplet Microfluidics Platform for Highly Sensitive and Quantitative Detection of Malaria-Causing Plasmodium Parasites Based on Enzyme Activity Measurement

    Juul, Sissel; Nielsen, Christine Juul Fælled; Labouriau, Rodrigo

    2012-01-01

    detectable at the single-molecule level. Combined with a droplet microfluidics lab-on-a-chip platform, this design allowed for sensitive, specific, and quantitative detection of all human-malaria-causing Plasmodium species in single drops of unprocessed blood with a detection limit of less than one parasite....../μL. Moreover, the setup allowed for detection of Plasmodium parasites in noninvasive saliva samples from infected patients. During recent years malaria transmission has declined worldwide, and with this the number of patients with low-parasite density has increased. Consequently, the need for accurate...

  7. Prevalence of Malaria Parasites in Hospitals of Portharcourt ...

    This investigation was conducted between March and July, 2010 in Portharcourt metropolis, Rivers State, Nigeria. The method of diagnosis utilised by the hospitals, clinics, and diagnostic laboratories was thick and thin method and malaria parasite was identified using standard criteria. In all the zones of the study, high ...

  8. Malaria Parasite Metabolic Pathways (MPMP) Upgraded with Targeted Chemical Compounds

    Ginsburg, Hagai

    2015-10-31

    Malaria Parasite Metabolic Pathways (MPMP) is the website for the functional genomics of intraerythrocytic Plasmodium falciparum. All the published information about targeted chemical compounds has now been added. Users can find the drug target and publication details linked to a drug database for further information about the medicinal properties of each compound.

  9. Malaria Parasite Metabolic Pathways (MPMP) Upgraded with Targeted Chemical Compounds

    Ginsburg, Hagai; Abdel-Haleem, Alyaa M.

    2015-01-01

    Malaria Parasite Metabolic Pathways (MPMP) is the website for the functional genomics of intraerythrocytic Plasmodium falciparum. All the published information about targeted chemical compounds has now been added. Users can find the drug target and publication details linked to a drug database for further information about the medicinal properties of each compound.

  10. Malaria Parasite Metabolic Pathways (MPMP) Upgraded with Targeted Chemical Compounds.

    Ginsburg, Hagai; Abdel-Haleem, Alyaa M

    2016-01-01

    Malaria Parasite Metabolic Pathways (MPMP) is the website for the functional genomics of intraerythrocytic Plasmodium falciparum. All the published information about targeted chemical compounds has now been added. Users can find the drug target and publication details linked to a drug database for further information about the medicinal properties of each compound. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Prevalence of malaria parasites and anaemia in pregnant and non ...

    A study of the prevalence of Malaria parasites in pregnant women attending pre - natal care in Government hospitals in two major towns (Aba and Okigwe) in Southeast Ngeria was carried out.Blood was collected by vein puncture rom 500 pregnant women in different trimesters (300 from Aba and 200 from Okigwe) and 200 ...

  12. Prevalence of Malaria Parasites among Nnamdi Azikwe University ...

    The prevalence of malaria parasites and antimalarial drug of choice wereinvestigated among students of Nnamdi Azikiwe University, Awka, Anambra State between February and May, 2008. A total of 800 blood samples were randomly collected from students aged 17-31 years. Thick films were prepared and microscopic ...

  13. PCR detection of malaria parasites in desiccated Anopheles mosquitoes is uninhibited by storage time and temperature

    Rider Mark A

    2012-06-01

    Full Text Available Abstract Background Reliable methods to preserve mosquito vectors for malaria studies are necessary for detecting Plasmodium parasites. In field settings, however, maintaining a cold chain of storage from the time of collection until laboratory processing, or accessing other reliable means of sample preservation is often logistically impractical or cost prohibitive. As the Plasmodium infection rate of Anopheles mosquitoes is a central component of the entomological inoculation rate and other indicators of transmission intensity, storage conditions that affect pathogen detection may bias malaria surveillance indicators. This study investigated the effect of storage time and temperature on the ability to detect Plasmodium parasites in desiccated Anopheles mosquitoes by real-time polymerase chain reaction (PCR. Methods Laboratory-infected Anopheles stephensi mosquitoes were chloroform-killed and stored over desiccant for 0, 1, 3, and 6 months while being held at four different temperatures: 28, 37, -20 and -80°C. The detection of Plasmodium DNA was evaluated by real-time PCR amplification of a 111 base pair region of block 4 of the merozoite surface protein. Results Varying the storage time and temperature of desiccated mosquitoes did not impact the sensitivity of parasite detection. A two-way factorial analysis of variance suggested that storage time and temperature were not associated with a loss in the ability to detect parasites. Storage of samples at 28°C resulted in a significant increase in the ability to detect parasite DNA, though no other positive associations were observed between the experimental storage treatments and PCR amplification. Conclusions Cold chain maintenance of desiccated mosquito samples is not necessary for real-time PCR detection of parasite DNA. Though field-collected mosquitoes may be subjected to variable conditions prior to molecular processing, the storage of samples over an inexpensive and logistically

  14. Evaluation of a novel magneto-optical method for the detection of malaria parasites.

    Agnes Orbán

    Full Text Available Improving the efficiency of malaria diagnosis is one of the main goals of current malaria research. We have recently developed a magneto-optical (MO method which allows high-sensitivity detection of malaria pigment (hemozoin crystals in blood via the magnetically induced rotational motion of the hemozoin crystals. Here, we evaluate this MO technique for the detection of Plasmodium falciparum in infected erythrocytes using in-vitro parasite cultures covering the entire intraerythrocytic life cycle. Our novel method detected parasite densities as low as ∼ 40 parasites per microliter of blood (0.0008% parasitemia at the ring stage and less than 10 parasites/µL (0.0002% parasitemia in the case of the later stages. These limits of detection, corresponding to approximately 20 pg/µL of hemozoin produced by the parasites, exceed that of rapid diagnostic tests and compete with the threshold achievable by light microscopic observation of blood smears. The MO diagnosis requires no special training of the operator or specific reagents for parasite detection, except for an inexpensive lysis solution to release intracellular hemozoin. The devices can be designed to a portable format for clinical and in-field tests. Besides testing its diagnostic performance, we also applied the MO technique to investigate the change in hemozoin concentration during parasite maturation. Our preliminary data indicate that this method may offer an efficient tool to determine the amount of hemozoin produced by the different parasite stages in synchronized cultures. Hence, it could eventually be used for testing the susceptibility of parasites to antimalarial drugs.

  15. Severe malaria is associated with parasite binding to endothelial protein C receptor

    Turner, Louise; Lavstsen, Thomas; Berger, Sanne S

    2013-01-01

    Sequestration of Plasmodium falciparum-infected erythrocytes in host blood vessels is a key triggering event in the pathogenesis of severe childhood malaria, which is responsible for about one million deaths every year. Sequestration is mediated by specific interactions between members of the P....... falciparum erythrocyte membrane protein 1 (PfEMP1) family and receptors on the endothelial lining. Severe childhood malaria is associated with expression of specific PfEMP1 subtypes containing domain cassettes (DCs) 8 and 13 (ref. 3), but the endothelial receptor for parasites expressing these proteins...

  16. Helminth-infected patients with malaria: a low profile transmission hub?

    Nacher Mathieu

    2012-11-01

    Full Text Available Abstract Eclipsed by the debates about malaria incidence and severity in individual patients, malaria transmission in helminth-infected persons has so far received very little attention. Studies in humans have shown increased malaria incidence and prevalence, and a trend for a reduction of symptoms in patients with malaria. This suggests that such patients could possibly be less likely to seek treatment thus carrying malaria parasites and their gametocytes for longer durations, therefore, being a greater potential source of transmission. In addition, in humans, a study showed increased gametocyte carriage, and in an animal model of helminth-malaria co-infection, there was increased malaria transmission. These elements converge towards the hypothesis that patients co-infected with worms and malaria may represent a hub of malaria transmission. The test of this hypothesis requires verifying, in different epidemiological settings, that helminth-infected patients have more gametocytes, that they have less symptomatic malaria and longer-lasting infections, and that they are more attractive for the vectors. The negative outcome in one setting of one of the above aspects does not necessarily mean that the other two aspects may suffice to increase transmission. If it is verified that patients co-infected by worms and malaria could be a transmission hub, this would be an interesting piece of strategic information in the context of the spread of anti-malarial resistance and the malaria eradication attempts.

  17. Helminth-infected patients with malaria: a low profile transmission hub?

    Nacher, Mathieu

    2012-11-15

    Eclipsed by the debates about malaria incidence and severity in individual patients, malaria transmission in helminth-infected persons has so far received very little attention. Studies in humans have shown increased malaria incidence and prevalence, and a trend for a reduction of symptoms in patients with malaria. This suggests that such patients could possibly be less likely to seek treatment thus carrying malaria parasites and their gametocytes for longer durations, therefore, being a greater potential source of transmission. In addition, in humans, a study showed increased gametocyte carriage, and in an animal model of helminth-malaria co-infection, there was increased malaria transmission. These elements converge towards the hypothesis that patients co-infected with worms and malaria may represent a hub of malaria transmission. The test of this hypothesis requires verifying, in different epidemiological settings, that helminth-infected patients have more gametocytes, that they have less symptomatic malaria and longer-lasting infections, and that they are more attractive for the vectors. The negative outcome in one setting of one of the above aspects does not necessarily mean that the other two aspects may suffice to increase transmission. If it is verified that patients co-infected by worms and malaria could be a transmission hub, this would be an interesting piece of strategic information in the context of the spread of anti-malarial resistance and the malaria eradication attempts.

  18. Lysophosphatidylcholine Regulates Sexual Stage Differentiation in the Human Malaria Parasite Plasmodium falciparum.

    Brancucci, Nicolas M B; Gerdt, Joseph P; Wang, ChengQi; De Niz, Mariana; Philip, Nisha; Adapa, Swamy R; Zhang, Min; Hitz, Eva; Niederwieser, Igor; Boltryk, Sylwia D; Laffitte, Marie-Claude; Clark, Martha A; Grüring, Christof; Ravel, Deepali; Blancke Soares, Alexandra; Demas, Allison; Bopp, Selina; Rubio-Ruiz, Belén; Conejo-Garcia, Ana; Wirth, Dyann F; Gendaszewska-Darmach, Edyta; Duraisingh, Manoj T; Adams, John H; Voss, Till S; Waters, Andrew P; Jiang, Rays H Y; Clardy, Jon; Marti, Matthias

    2017-12-14

    Transmission represents a population bottleneck in the Plasmodium life cycle and a key intervention target of ongoing efforts to eradicate malaria. Sexual differentiation is essential for this process, as only sexual parasites, called gametocytes, are infective to the mosquito vector. Gametocyte production rates vary depending on environmental conditions, but external stimuli remain obscure. Here, we show that the host-derived lipid lysophosphatidylcholine (LysoPC) controls P. falciparum cell fate by repressing parasite sexual differentiation. We demonstrate that exogenous LysoPC drives biosynthesis of the essential membrane component phosphatidylcholine. LysoPC restriction induces a compensatory response, linking parasite metabolism to the activation of sexual-stage-specific transcription and gametocyte formation. Our results reveal that malaria parasites can sense and process host-derived physiological signals to regulate differentiation. These data close a critical knowledge gap in parasite biology and introduce a major component of the sexual differentiation pathway in Plasmodium that may provide new approaches for blocking malaria transmission. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  19. Helminths and malaria co-infections are associated with elevated serum IgE

    Mulu, Andargachew; Kassu, Afework; Legesse, Mengistu

    2014-01-01

    BACKGROUND: Both helminth and malaria infections result in a highly polarized immune response characterized by IgE production. This study aimed to investigate the total serum IgE profile in vivo as a measure of Th2 immune response in malaria patients with and without helminth co-infection. METHODS......: A cross sectional observational study composed of microscopically confirmed malaria positive (N = 197) and malaria negative (N = 216) apparently healthy controls with and without helminth infection was conducted at Wondo Genet Health Center, Southern Ethiopia. A pre-designed structured format was utilized...... to collect socio-demographic and clinical data of the subjects. Detection and quantification of helminths, malaria parasites and determination of serum IgE levels were carried out following standard procedures. RESULTS: Irrespective of helminth infection, individuals infected by malaria showed significantly...

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

    Reece Sarah E

    2008-09-01

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

  1. Stress and sex in malaria parasites: Why does commitment vary?

    Carter, Lucy M; Kafsack, Björn F C; Llinás, Manuel; Mideo, Nicole; Pollitt, Laura C; Reece, Sarah E

    2013-01-01

    For vector-borne parasites such as malaria, how within- and between-host processes interact to shape transmission is poorly understood. In the host, malaria parasites replicate asexually but for transmission to occur, specialized sexual stages (gametocytes) must be produced. Despite the central role that gametocytes play in disease transmission, explanations of why parasites adjust gametocyte production in response to in-host factors remain controversial. We propose that evolutionary theory developed to explain variation in reproductive effort in multicellular organisms, provides a framework to understand gametocyte investment strategies. We examine why parasites adjust investment in gametocytes according to the impact of changing conditions on their in-host survival. We then outline experiments required to determine whether plasticity in gametocyte investment enables parasites to maintain fitness in a variable environment. Gametocytes are a target for anti-malarial transmission-blocking interventions so understanding plasticity in investment is central to maximizing the success of control measures in the face of parasite evolution.

  2. Malaria infections in crews of Japanese ships.

    Shoda, M; Shimizu, K; Nagano, M; Ishii, M

    2001-01-01

    Plasmodium falciparum malaria is the most dangerous infection for seafarers in West Africa. In December 1998, five cases of this infection occurred among Japanese seafarers in West Africa, two of them died, one on board ship, and another died five days after the admission to the hospital in Reunion island, East Africa. Six other cases of falciparum malaria infection occurred among Japanese seafarers on another ship in December 1999. Three infected persons were admitted to hospitals in Abidjan (Ivory Coast) and Point Noire (Congo). In Japan, over 100 cases of imported malaria were recorded each year during the period from 1990 to 1997, and about 40% of these cases were falciparum infections. It is not known how many of them occurred among seafarers. We estimate that at least 5% of all malaria cases in Japan are seafarers. Measures to protect crews of ships against malaria are discussed.

  3. A Network Approach to Analyzing Highly Recombinant Malaria Parasite Genes

    Larremore, Daniel B.; Clauset, Aaron; Buckee, Caroline O.

    2013-01-01

    The var genes of the human malaria parasite Plasmodium falciparum present a challenge to population geneticists due to their extreme diversity, which is generated by high rates of recombination. These genes encode a primary antigen protein called PfEMP1, which is expressed on the surface of infected red blood cells and elicits protective immune responses. Var gene sequences are characterized by pronounced mosaicism, precluding the use of traditional phylogenetic tools that require bifurcating tree-like evolutionary relationships. We present a new method that identifies highly variable regions (HVRs), and then maps each HVR to a complex network in which each sequence is a node and two nodes are linked if they share an exact match of significant length. Here, networks of var genes that recombine freely are expected to have a uniformly random structure, but constraints on recombination will produce network communities that we identify using a stochastic block model. We validate this method on synthetic data, showing that it correctly recovers populations of constrained recombination, before applying it to the Duffy Binding Like-α (DBLα) domain of var genes. We find nine HVRs whose network communities map in distinctive ways to known DBLα classifications and clinical phenotypes. We show that the recombinational constraints of some HVRs are correlated, while others are independent. These findings suggest that this micromodular structuring facilitates independent evolutionary trajectories of neighboring mosaic regions, allowing the parasite to retain protein function while generating enormous sequence diversity. Our approach therefore offers a rigorous method for analyzing evolutionary constraints in var genes, and is also flexible enough to be easily applied more generally to any highly recombinant sequences. PMID:24130474

  4. A network approach to analyzing highly recombinant malaria parasite genes.

    Larremore, Daniel B; Clauset, Aaron; Buckee, Caroline O

    2013-01-01

    The var genes of the human malaria parasite Plasmodium falciparum present a challenge to population geneticists due to their extreme diversity, which is generated by high rates of recombination. These genes encode a primary antigen protein called PfEMP1, which is expressed on the surface of infected red blood cells and elicits protective immune responses. Var gene sequences are characterized by pronounced mosaicism, precluding the use of traditional phylogenetic tools that require bifurcating tree-like evolutionary relationships. We present a new method that identifies highly variable regions (HVRs), and then maps each HVR to a complex network in which each sequence is a node and two nodes are linked if they share an exact match of significant length. Here, networks of var genes that recombine freely are expected to have a uniformly random structure, but constraints on recombination will produce network communities that we identify using a stochastic block model. We validate this method on synthetic data, showing that it correctly recovers populations of constrained recombination, before applying it to the Duffy Binding Like-α (DBLα) domain of var genes. We find nine HVRs whose network communities map in distinctive ways to known DBLα classifications and clinical phenotypes. We show that the recombinational constraints of some HVRs are correlated, while others are independent. These findings suggest that this micromodular structuring facilitates independent evolutionary trajectories of neighboring mosaic regions, allowing the parasite to retain protein function while generating enormous sequence diversity. Our approach therefore offers a rigorous method for analyzing evolutionary constraints in var genes, and is also flexible enough to be easily applied more generally to any highly recombinant sequences.

  5. A network approach to analyzing highly recombinant malaria parasite genes.

    Daniel B Larremore

    Full Text Available The var genes of the human malaria parasite Plasmodium falciparum present a challenge to population geneticists due to their extreme diversity, which is generated by high rates of recombination. These genes encode a primary antigen protein called PfEMP1, which is expressed on the surface of infected red blood cells and elicits protective immune responses. Var gene sequences are characterized by pronounced mosaicism, precluding the use of traditional phylogenetic tools that require bifurcating tree-like evolutionary relationships. We present a new method that identifies highly variable regions (HVRs, and then maps each HVR to a complex network in which each sequence is a node and two nodes are linked if they share an exact match of significant length. Here, networks of var genes that recombine freely are expected to have a uniformly random structure, but constraints on recombination will produce network communities that we identify using a stochastic block model. We validate this method on synthetic data, showing that it correctly recovers populations of constrained recombination, before applying it to the Duffy Binding Like-α (DBLα domain of var genes. We find nine HVRs whose network communities map in distinctive ways to known DBLα classifications and clinical phenotypes. We show that the recombinational constraints of some HVRs are correlated, while others are independent. These findings suggest that this micromodular structuring facilitates independent evolutionary trajectories of neighboring mosaic regions, allowing the parasite to retain protein function while generating enormous sequence diversity. Our approach therefore offers a rigorous method for analyzing evolutionary constraints in var genes, and is also flexible enough to be easily applied more generally to any highly recombinant sequences.

  6. Regulatory hotspots in the malaria parasite genome dictate transcriptional variation.

    Joseph M Gonzales

    2008-09-01

    Full Text Available The determinants of transcriptional regulation in malaria parasites remain elusive. The presence of a well-characterized gene expression cascade shared by different Plasmodium falciparum strains could imply that transcriptional regulation and its natural variation do not contribute significantly to the evolution of parasite drug resistance. To clarify the role of transcriptional variation as a source of stain-specific diversity in the most deadly malaria species and to find genetic loci that dictate variations in gene expression, we examined genome-wide expression level polymorphisms (ELPs in a genetic cross between phenotypically distinct parasite clones. Significant variation in gene expression is observed through direct co-hybridizations of RNA from different P. falciparum clones. Nearly 18% of genes were regulated by a significant expression quantitative trait locus. The genetic determinants of most of these ELPs resided in hotspots that are physically distant from their targets. The most prominent regulatory locus, influencing 269 transcripts, coincided with a Chromosome 5 amplification event carrying the drug resistance gene, pfmdr1, and 13 other genes. Drug selection pressure in the Dd2 parental clone lineage led not only to a copy number change in the pfmdr1 gene but also to an increased copy number of putative neighboring regulatory factors that, in turn, broadly influence the transcriptional network. Previously unrecognized transcriptional variation, controlled by polymorphic regulatory genes and possibly master regulators within large copy number variants, contributes to sweeping phenotypic evolution in drug-resistant malaria parasites.

  7. Eosinophilic fasciitis after parasite infection

    Marta Oliveira

    2016-03-01

    Full Text Available Eosinophilic fasciitis is a systemic inflammatory disease characterized by symmetrical swelling and skin induration of the distal portions of the arms and/or legs, evolving into a scleroderma-like appearance, accompanied by peripheral blood eosinophilia. It is a rare disease with a poorly understood etiology. Corticosteroid treatment remains the standard therapy, either taken alone or in association with an immunosuppressive drug. This paper presents a case of a male patient with palpebral edema and marked eosinophilia, diagnosed with intestinal parasitic infection in October 2006. He was treated with an antiparasitic drug, but both the swelling and the analytical changes remained. This was followed by a skin and muscle biopsy, which turned out to be compatible with eosinophilic fasciitis. There was progressive worsening of the clinical state, with stiffness of the abdominal wall and elevated inflammatory parameters, and the patient was referred to the Immunology Department, medicated with corticosteroids and methotrexate. Over the years there were therapeutic adjustments and other causes were excluded. Currently the patient continues to be monitored, and there is no evidence of active disease. The case described in this article is interesting because of the diagnosis of eosinophilic fasciitis probably associated/coexisting with a parasite infection. This case report differs from others in that there is an uncommon cause associated with the onset of the disease, instead of the common causes such as trauma, medication, non-parasitic infections or cancer.

  8. Schistosoma mansoni infection suppresses the growth of Plasmodium yoelii parasites in the liver and reduces gametocyte infectivity to mosquitoes.

    Taeko Moriyasu

    2018-01-01

    Full Text Available Malaria and schistosomiasis are major parasitic diseases causing morbidity and mortality in the tropics. Epidemiological surveys have revealed coinfection rates of up to 30% among children in Sub-Saharan Africa. To investigate the impact of coinfection of these two parasites on disease epidemiology and pathology, we carried out coinfection studies using Plasmodium yoelii and Schistosoma mansoni in mice. Malaria parasite growth in the liver following sporozoite inoculation is significantly inhibited in mice infected with S. mansoni, so that when low numbers of sporozoites are inoculated, there is a large reduction in the percentage of mice that go on to develop blood stage malaria. Furthermore, gametocyte infectivity is much reduced in mice with S. mansoni infections. These results have profound implications for understanding the interactions between Plasmodium and Schistosoma species, and have implications for the control of malaria in schistosome endemic areas.

  9. Malaria case clinical profiles and Plasmodium falciparum parasite genetic diversity: a cross sectional survey at two sites of different malaria transmission intensities in Rwanda.

    Kateera, Fredrick; Nsobya, Sam L; Tukwasibwe, Stephen; Mens, Petra F; Hakizimana, Emmanuel; Grobusch, Martin P; Mutesa, Leon; Kumar, Nirbhay; van Vugt, Michele

    2016-04-26

    Malaria remains a public health challenge in sub-Saharan Africa with Plasmodium falciparum being the principal cause of malaria disease morbidity and mortality. Plasmodium falciparum virulence is attributed, in part, to its population-level genetic diversity-a characteristic that has yet to be studied in Rwanda. Characterizing P. falciparum molecular epidemiology in an area is needed for a better understand of malaria transmission and to inform choice of malaria control strategies. In this health-facility based survey, malaria case clinical profiles and parasite densities as well as parasite genetic diversity were compared among P. falciparum-infected patients identified at two sites of different malaria transmission intensities in Rwanda. Data on demographics and clinical features and finger-prick blood samples for microscopy and parasite genotyping were collected(.) Nested PCR was used to genotype msp-2 alleles of FC27 and 3D7. Patients' variables of age group, sex, fever (both by patient report and by measured tympanic temperatures), parasite density, and bed net use were found differentially distributed between the higher endemic (Ruhuha) and lower endemic (Mubuga) sites. Overall multiplicity of P. falciparum infection (MOI) was 1.73 but with mean MOI found to vary significantly between 2.13 at Ruhuha and 1.29 at Mubuga (p < 0.0001). At Ruhuha, expected heterozygosity (EH) for FC27 and 3D7 alleles were 0.62 and 0.49, respectively, whilst at Mubuga, EH for FC27 and 3D7 were 0.26 and 0.28, respectively. In this study, a higher geometrical mean parasite counts, more polyclonal infections, higher MOI, and higher allelic frequency were observed at the higher malaria-endemic (Ruhuha) compared to the lower malaria-endemic (Mubuga) area. These differences in malaria risk and MOI should be considered when choosing setting-specific malaria control strategies, assessing p. falciparum associated parameters such as drug resistance, immunity and impact of used

  10. Genome sequencing of chimpanzee malaria parasites reveals possible pathways of adaptation to human hosts

    Otto, Thomas D.

    2014-09-09

    Plasmodium falciparum causes most human malaria deaths, having prehistorically evolved from parasites of African Great Apes. Here we explore the genomic basis of P. falciparum adaptation to human hosts by fully sequencing the genome of the closely related chimpanzee parasite species P. reichenowi, and obtaining partial sequence data from a more distantly related chimpanzee parasite (P. gaboni). The close relationship between P. reichenowi and P. falciparum is emphasized by almost complete conservation of genomic synteny, but against this strikingly conserved background we observe major differences at loci involved in erythrocyte invasion. The organization of most virulence-associated multigene families, including the hypervariable var genes, is broadly conserved, but P. falciparum has a smaller subset of rif and stevor genes whose products are expressed on the infected erythrocyte surface. Genome-wide analysis identifies other loci under recent positive selection, but a limited number of changes at the host–parasite interface may have mediated host switching.

  11. Comparative Genomics and Systems Biology of Malaria Parasites Plasmodium

    Cai, Hong; Zhou, Zhan; Gu, Jianying; Wang, Yufeng

    2013-01-01

    Malaria is a serious infectious disease that causes over one million deaths yearly. It is caused by a group of protozoan parasites in the genus Plasmodium. No effective vaccine is currently available and the elevated levels of resistance to drugs in use underscore the pressing need for novel antimalarial targets. In this review, we survey omics centered developments in Plasmodium biology, which have set the stage for a quantum leap in our understanding of the fundamental processes of the parasite life cycle and mechanisms of drug resistance and immune evasion. PMID:24298232

  12. Nuclear techniques in the study of parasitic infections

    1982-01-01

    Out of 57 papers published, 47 fall within the INIS subject scope. Seven main topics were covered: resistance to infections with protozoan parasites; resistance to infections with African trypanosomes and helminths of ruminant animals; resistance to infections with filarial parasites and schistosomes; pathology of parasitic infections; epidemiology and diagnosis of parasitic infections; physiology and biochemistry of parasitic organisms; pharmacodynamics of anti-parasitic agents

  13. Sex and death: the effects of innate immune factors on the sexual reproduction of malaria parasites.

    Ricardo S Ramiro

    2011-03-01

    Full Text Available Malaria parasites must undergo a round of sexual reproduction in the blood meal of a mosquito vector to be transmitted between hosts. Developing a transmission-blocking intervention to prevent parasites from mating is a major goal of biomedicine, but its effectiveness could be compromised if parasites can compensate by simply adjusting their sex allocation strategies. Recently, the application of evolutionary theory for sex allocation has been supported by experiments demonstrating that malaria parasites adjust their sex ratios in response to infection genetic diversity, precisely as predicted. Theory also predicts that parasites should adjust sex allocation in response to host immunity. Whilst data are supportive, the assumptions underlying this prediction - that host immune responses have differential effects on the mating ability of males and females - have not yet been tested. Here, we combine experimental work with theoretical models in order to investigate whether the development and fertility of male and female parasites is affected by innate immune factors and develop new theory to predict how parasites' sex allocation strategies should evolve in response to the observed effects. Specifically, we demonstrate that reactive nitrogen species impair gametogenesis of males only, but reduce the fertility of both male and female gametes. In contrast, tumour necrosis factor-α does not influence gametogenesis in either sex but impairs zygote development. Therefore, our experiments demonstrate that immune factors have complex effects on each sex, ranging from reducing the ability of gametocytes to develop into gametes, to affecting the viability of offspring. We incorporate these results into theory to predict how the evolutionary trajectories of parasite sex ratio strategies are shaped by sex differences in gamete production, fertility and offspring development. We show that medical interventions targeting offspring development are more likely

  14. Enlightening the malaria parasite life cycle: bioluminescent Plasmodium in fundamental and applied research

    Siciliano, Giulia; Alano, Pietro

    2015-01-01

    The unicellular protozoan parasites of the genus Plasmodium impose on human health worldwide the enormous burden of malaria. The possibility to genetically modify several species of malaria parasites represented a major advance in the possibility to elucidate their biology and is now turning laboratory lines of transgenic Plasmodium into precious weapons to fight malaria. Amongst the various genetically modified plasmodia, transgenic parasite lines expressing bioluminescent reporters have bee...

  15. Parasitic infections of the external eye.

    Pahuja, Shivani; Puranik, Charuta; Jelliti, Bechir; Khairallah, Moncef; Sangwan, Virender S

    2013-08-01

    To review the published literature on parasitic infections of external eye. Published articles and case reports on parasitic infections of external eye were reviewed and relevant information was collected. Parasitic infections of the eye are rare. However, being more commonly seen in developing nations, they require active measures for screening, diagnosis, and therapy. Parasites of importance causing external ocular disease are protozoan parasites, such as Leishmania; metazoans, such as nematodes (roundworms), cestodes (tapeworms), and trematodes (flatworms); or ectoparasites, such as Phthirus pubis and Demodex.

  16. Possible biochemical impact of malaria infection in subjects with HIV co-infection in Anambra state, Nigeria.

    Onyenekwe, C C; Ukibe, N; Meludu, S C; Ifeanyi, M; Ezeani, M; Onochie, A; Ofiaeli, N; Aboh, N; Ilika, A

    2008-06-01

    The present study was designed to determine possible contributory impact of malaria infection on some biochemical markers in subjects with HIV co-infection in order to know if they are adverse or protective. Participants were recruited at the Voluntary Counseling and Testing Unit, Nnamdi Azikiwe University Teaching Hospital, Nnewi, Nigeria and grouped into: (i) Malaria and HIV co-infection group (n = 45); and (ii) HIV infected group without concurrent malaria infection (n = 57). Standard laboratory methods were used for the HIV and Plasmodium falciparum antigen screening, malaria parasite density, CD4+ T-cell count, packed cell volume, white blood cell count, serum iron and albumin concentrations. The results showed that serum iron and albumin were significantly reduced and raised respectively in 'Malaria-HIV co-infection group' compared with 'HIV infection group' (p < 0.05 and p < 0.05). A positive association was observed between age and serum iron concentration in malaria and HIV co-infected group (r = 0.580; p < 0.05) while negative associations were observed between PCV and serum iron (r = - 0.388; p < 0.05) and between CD4+ T-cells and serum iron concentration (r = -0.362; p < 0.05) in malaria and HIV co-infected group. The CD4+ T-cell count, WBC count, PCV were not significantly different between the Malaria-HIV co-infection group and HIV infection group. In the present study serum iron and albumin concentrations were the most sensitive indicators that showed the contributory impact of malaria infection on biochemical index in HIV co-infected subjects. The findings suggest that at the defined stage of HIV infection in the present study, malaria co-infection may moderate the impact of HIV infection on iron metabolism and hepatic synthesis of albumin.

  17. Rethinking the extrinsic incubation period of malaria parasites.

    Ohm, Johanna R; Baldini, Francesco; Barreaux, Priscille; Lefevre, Thierry; Lynch, Penelope A; Suh, Eunho; Whitehead, Shelley A; Thomas, Matthew B

    2018-03-12

    The time it takes for malaria parasites to develop within a mosquito, and become transmissible, is known as the extrinsic incubation period, or EIP. EIP is a key parameter influencing transmission intensity as it combines with mosquito mortality rate and competence to determine the number of mosquitoes that ultimately become infectious. In spite of its epidemiological significance, data on EIP are scant. Current approaches to estimate EIP are largely based on temperature-dependent models developed from data collected on parasite development within a single mosquito species in the 1930s. These models assume that the only factor affecting EIP is mean environmental temperature. Here, we review evidence to suggest that in addition to mean temperature, EIP is likely influenced by genetic diversity of the vector, diversity of the parasite, and variation in a range of biotic and abiotic factors that affect mosquito condition. We further demonstrate that the classic approach of measuring EIP as the time at which mosquitoes first become infectious likely misrepresents EIP for a mosquito population. We argue for a better understanding of EIP to improve models of transmission, refine predictions of the possible impacts of climate change, and determine the potential evolutionary responses of malaria parasites to current and future mosquito control tools.

  18. Comparison of clinical and parasitological data from controlled human malaria infection trials.

    Meta Roestenberg

    Full Text Available Exposing healthy human volunteers to Plasmodium falciparum-infected mosquitoes is an accepted tool to evaluate preliminary efficacy of malaria vaccines. To accommodate the demand of the malaria vaccine pipeline, controlled infections are carried out in an increasing number of centers worldwide. We assessed their safety and reproducibility.We reviewed safety and parasitological data from 128 malaria-naïve subjects participating in controlled malaria infection trials conducted at the University of Oxford, UK, and the Radboud University Nijmegen Medical Center, The Netherlands. Results were compared to a report from the US Military Malaria Vaccine Program.We show that controlled human malaria infection trials are safe and demonstrate a consistent safety profile with minor differences in the frequencies of arthralgia, fatigue, chills and fever between institutions. But prepatent periods show significant variation. Detailed analysis of Q-PCR data reveals highly synchronous blood stage parasite growth and multiplication rates.Procedural differences can lead to some variation in safety profile and parasite kinetics between institutions. Further harmonization and standardization of protocols will be useful for wider adoption of these cost-effective small-scale efficacy trials. Nevertheless, parasite growth rates are highly reproducible, illustrating the robustness of controlled infections as a valid tool for malaria vaccine development.

  19. The Puf-family RNA-binding protein Puf2 controls sporozoite conversion to liver stages in the malaria parasite.

    Katja Müller

    Full Text Available Malaria is a vector-borne infectious disease caused by unicellular, obligate intracellular parasites of the genus Plasmodium. During host switch the malaria parasite employs specialized latent stages that colonize the new host environment. Previous work has established that gametocytes, sexually differentiated stages that are taken up by the mosquito vector, control expression of genes required for mosquito colonization by translational repression. Sexual parasite development is controlled by a DEAD-box RNA helicase of the DDX6 family, termed DOZI. Latency of sporozoites, the transmission stage injected during an infectious blood meal, is controlled by the eIF2alpha kinase IK2, a general inhibitor of protein synthesis. Whether RNA-binding proteins participate in translational regulation in sporozoites remains to be studied. Here, we investigated the roles of two RNA-binding proteins of the Puf-family, Plasmodium Puf1 and Puf2, during sporozoite stage conversion. Our data reveal that, in the rodent malaria parasite P. berghei, Puf2 participates in the regulation of IK2 and inhibits premature sporozoite transformation. Inside mosquito salivary glands puf2⁻ sporozoites transform over time to round forms resembling early intra-hepatic stages. As a result, mutant parasites display strong defects in initiating a malaria infection. In contrast, Puf1 is dispensable in vivo throughout the entire Plasmodium life cycle. Our findings support the notion of a central role for Puf2 in parasite latency during switch between the insect and mammalian hosts.

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

    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

  1. Does Magnetic Field Affect Malaria Parasite Replication in Human Red Blood Cells?

    Chanturiya, Alexandr N.; Glushakova, Svetlana; Yin, Dan; Zimmerberg, Joshua

    2004-01-01

    Digestion of red blood cell (RBC) hemoglobin by the malaria parasite results in the formation of paramagnetic hemazoin crystals inside the parasite body. A number of reports suggest that magnetic field interaction with hamazoin crystals significantly reduces the number of infected cells in culture, and thus magnetic field can be used to combat malaria. We studies the effects of magnetic filed on the Plasmodium falciparum asexual life cycle inside RBCs under various experimental conditions. No effect was found during prolonged exposure of infected RBCs to constant magnetic fields up to 6000 Gauss. Infected RBCs were also exposed, under temperature-controlled conditions, to oscillating magnetic fields with frequencies in the range of 500-20000 kHz, and field strength 30-600 Gauss. This exposure often changed the proportion of different parasite stages in treated culture compared to controls. However, no significant effect on parasitemia was observed in treated cultures. This result indicates that the magnetic field effect on Plasmodium falciparum is negligible, or that hypothetical negative and positive effects on different stages within one 48-hour compensate each other.

  2. CHEMOTHERAPY, WITHIN-HOST ECOLOGY AND THE FITNESS OF DRUG-RESISTANT MALARIA PARASITES

    Huijben, Silvie; Nelson, William A.; Wargo, Andrew R.; Sim, Derek G.; Drew, Damien R.; Read, Andrew F.

    2010-01-01

    A major determinant of the rate at which drug-resistant malaria parasites spread through a population is the ecology of resistant and sensitive parasites sharing the same host. Drug treatment can significantly alter this ecology by removing the drug-sensitive parasites, leading to competitive release of resistant parasites. Here, we test the hypothesis that the spread of resistance can be slowed by reducing drug treatment and hence restricting competitive release. Using the rodent malaria mod...

  3. Detection of malaria parasites by microscopy and rapid diagnostic ...

    The effectiveness of Rapid Diagnostic Test Kit (RDT) was compared with microscopy for the evaluation of malaria infection in children and pregnant women attending two selected health facilities in Lagos State, south-western, Nigeria. A total of 482 patients comprising 252 pregnant women (mean age: 26.86±4.46 years) ...

  4. Estimating Geographical Variation in the Risk of Zoonotic Plasmodium knowlesi Infection in Countries Eliminating Malaria.

    Freya M Shearer

    2016-08-01

    Full Text Available Infection by the simian malaria parasite, Plasmodium knowlesi, can lead to severe and fatal disease in humans, and is the most common cause of malaria in parts of Malaysia. Despite being a serious public health concern, the geographical distribution of P. knowlesi malaria risk is poorly understood because the parasite is often misidentified as one of the human malarias. Human cases have been confirmed in at least nine Southeast Asian countries, many of which are making progress towards eliminating the human malarias. Understanding the geographical distribution of P. knowlesi is important for identifying areas where malaria transmission will continue after the human malarias have been eliminated.A total of 439 records of P. knowlesi infections in humans, macaque reservoir and vector species were collated. To predict spatial variation in disease risk, a model was fitted using records from countries where the infection data coverage is high. Predictions were then made throughout Southeast Asia, including regions where infection data are sparse. The resulting map predicts areas of high risk for P. knowlesi infection in a number of countries that are forecast to be malaria-free by 2025 (Malaysia, Cambodia, Thailand and Vietnam as well as countries projected to be eliminating malaria (Myanmar, Laos, Indonesia and the Philippines.We have produced the first map of P. knowlesi malaria risk, at a fine-scale resolution, to identify priority areas for surveillance based on regions with sparse data and high estimated risk. Our map provides an initial evidence base to better understand the spatial distribution of this disease and its potential wider contribution to malaria incidence. Considering malaria elimination goals, areas for prioritised surveillance are identified.

  5. Targeting channels and transporters in protozoan parasite infections

    Meier, Anna; Erler, Holger; Beitz, Eric

    2018-03-01

    Infectious diseases caused by pathogenic protozoa are among the most significant causes of death in humans. Therapeutic options are scarce and massively challenged by the emergence of resistant parasite strains. Many of the current anti-parasite drugs target soluble enzymes, generate unspecific oxidative stress, or act by an unresolved mechanism within the parasite. In recent years, collections of drug-like compounds derived from large-scale phenotypic screenings, such as the malaria or pathogen box, have been made available to researchers free of charge boosting the identification of novel promising targets. Remarkably, several of the compound hits have been found to inhibit membrane proteins at the periphery of the parasites, i.e. channels and transporters for ions and metabolites. In this review, we will focus on the progress made on targeting channels and transporters at different levels and the potential for use against infections with apicomplexan parasites mainly Plasmodium spp. (malaria) and Toxoplasma gondii (toxoplasmosis), with kinetoplastids Trypanosoma brucei (sleeping sickness), Trypanosoma cruzi (Chagas disease) and Leishmania ssp. (leishmaniasis), and the amoeba Entamoeba histolytica (amoebiasis).

  6. High-Throughput Testing of Antibody-Dependent Binding Inhibition of Placental Malaria Parasites

    Nielsen, Morten A; Salanti, Ali

    2015-01-01

    The particular virulence of Plasmodium falciparum manifests in diverse severe malaria syndromes as cerebral malaria, severe anemia and placental malaria. The cause of both the severity and the diversity of infection outcome, is the ability of the infected erythrocyte (IE) to bind a range......-throughput assay used in the preclinical and clinical development of a VAR2CSA based vaccine against placental malaria....

  7. Effectiveness of Gamma Rays in Attenuating Rodent Malaria Parasites of Plasmodium berghei in Blood of Mice

    Syaifudin, M.; Darlina; Rahardjo, T.; Tetriana, D.; Nurhayati, S.; Surniyantoro, H.N.E.; Kisnanto, T.

    2013-01-01

    Malaria is a major public health problem in Indonesia. Therefore, an effective vaccine against this disease is actively being sought by using gamma rays to attenuate the parasites. However, the safety and efficacy of the resulting vaccine are dependent on the precise irradiation dose. The aim of this research was to determine the exact time when the parasites are attenuated by gamma ray exposure. Mice blood containing Plasmodium berghei of 5,0 X 10 7 parasites/ml was irradiated with gamma rays at doses of 0, 150, 175 and 200 Gy (doses rate of 380 Gy/h) and then was injected intraperitoneally to mice at 0, 1, 2, 3, and 4 h post irradiation. The parasitemia (parasite density) in mouse blood was observed starting with day 2 and repeated every 2-4 days up to 28 days. The survival of the mice was also observed during the experiment. The results showed that the pre-patent period advanced with exposing infected blood to 150 and 175 Gy irradiations, suggesting some degree of attenuation. The amount of radiation required to render the parasites non-viable is about 175 Gy for an inoculum of a number of parasites, but a delay of 4 h resulted in the death of parasites. There was no difference in the infectivity of irradiated parasite injected 1 h and 2 h post irradiation in terms of parasitemia and the survival of mouse. For a dose of 200 Gy which was injected 2 h post irradiation, no parasitemia was found in the blood and animals which died after times varying from 1 to 4 weeks. We concluded that irradiated parasites should be injected into the host within 1 h after irradiation. (author)

  8. Signalling in malaria parasites – The MALSIG consortium#

    Doerig C.

    2009-09-01

    Full Text Available Depending on their developmental stage in the life cycle, malaria parasites develop within or outside host cells, and in extremely diverse contexts such as the vertebrate liver and blood circulation, or the insect midgut and hemocoel. Cellular and molecular mechanisms enabling the parasite to sense and respond to the intra- and the extra-cellular environments are therefore key elements for the proliferation and transmission of Plasmodium, and therefore are, from a public health perspective, strategic targets in the fight against this deadly disease. The MALSIG consortium, which was initiated in February 2009, was designed with the primary objective to integrate research ongoing in Europe and India on i the properties of Plasmodium signalling molecules, and ii developmental processes occurring at various points of the parasite life cycle. On one hand, functional studies of individual genes and their products in Plasmodium falciparum (and in the technically more manageable rodent model Plasmodium berghei are providing information on parasite protein kinases and phosphatases, and of the molecules governing cyclic nucleotide metabolism and calcium signalling. On the other hand, cellular and molecular studies are elucidating key steps of parasite development such as merozoite invasion and egress in blood and liver parasite stages, control of DNA replication in asexual and sexual development, membrane dynamics and trafficking, production of gametocytes in the vertebrate host and further parasite development in the mosquito. This article, which synthetically reviews such signalling molecules and cellular processes, aims to provide a glimpse of the global frame in which the activities of the MALSIG consortium will develop over the next three years.

  9. IP-10-mediated T cell homing promotes cerebral inflammation over splenic immunity to malaria infection.

    Catherine Q Nie

    2009-04-01

    Full Text Available Plasmodium falciparum malaria causes 660 million clinical cases with over 2 million deaths each year. Acquired host immunity limits the clinical impact of malaria infection and provides protection against parasite replication. Experimental evidence indicates that cell-mediated immune responses also result in detrimental inflammation and contribute to severe disease induction. In both humans and mice, the spleen is a crucial organ involved in blood stage malaria clearance, while organ-specific disease appears to be associated with sequestration of parasitized erythrocytes in vascular beds and subsequent recruitment of inflammatory leukocytes. Using a rodent model of cerebral malaria, we have previously found that the majority of T lymphocytes in intravascular infiltrates of cerebral malaria-affected mice express the chemokine receptor CXCR3. Here we investigated the effect of IP-10 blockade in the development of experimental cerebral malaria and the induction of splenic anti-parasite immunity. We found that specific neutralization of IP-10 over the course of infection and genetic deletion of this chemokine in knockout mice reduces cerebral intravascular inflammation and is sufficient to protect P. berghei ANKA-infected mice from fatality. Furthermore, our results demonstrate that lack of IP-10 during infection significantly reduces peripheral parasitemia. The increased resistance to infection observed in the absence of IP-10-mediated cell trafficking was associated with retention and subsequent expansion of parasite-specific T cells in spleens of infected animals, which appears to be advantageous for the control of parasite burden. Thus, our results demonstrate that modulating homing of cellular immune responses to malaria is critical for reaching a balance between protective immunity and immunopathogenesis.

  10. Normocyte-binding protein required for human erythrocyte invasion by the zoonotic malaria parasitePlasmodium knowlesi

    Moon, Robert W.; Sharaf, Hazem; Hastings, Claire H.; Ho, Yung Shwen; Nair, Mridul; Rchiad, ‍ Zineb; Knuepfer, Ellen; Ramaprasad, Abhinay; Mohring, Franziska; Amir, Amirah; Yusuf, Noor A.; Hall, Joanna; Almond, Neil; Lau, Yee Ling; Pain, Arnab; Blackman, Michael J.; Holder, Anthony A.

    2016-01-01

    The dominant cause of malaria in Malaysia is now Plasmodium knowlesi, a zoonotic parasite of cynomolgus macaque monkeys found throughout South East Asia. Comparative genomic analysis of parasites adapted to in vitro growth in either cynomolgus or human RBCs identified a genomic deletion that includes the gene encoding normocyte-binding protein Xa (NBPXa) in parasites growing in cynomolgus RBCs but not in human RBCs. Experimental deletion of the NBPXa gene in parasites adapted to growth in human RBCs (which retain the ability to grow in cynomolgus RBCs) restricted them to cynomolgus RBCs, demonstrating that this gene is selectively required for parasite multiplication and growth in human RBCs. NBPXa-null parasites could bind to human RBCs, but invasion of these cells was severely impaired. Therefore, NBPXa is identified as a key mediator of P. knowlesi human infection and may be a target for vaccine development against this emerging pathogen.

  11. Normocyte-binding protein required for human erythrocyte invasion by the zoonotic malaria parasitePlasmodium knowlesi

    Moon, Robert W.

    2016-06-15

    The dominant cause of malaria in Malaysia is now Plasmodium knowlesi, a zoonotic parasite of cynomolgus macaque monkeys found throughout South East Asia. Comparative genomic analysis of parasites adapted to in vitro growth in either cynomolgus or human RBCs identified a genomic deletion that includes the gene encoding normocyte-binding protein Xa (NBPXa) in parasites growing in cynomolgus RBCs but not in human RBCs. Experimental deletion of the NBPXa gene in parasites adapted to growth in human RBCs (which retain the ability to grow in cynomolgus RBCs) restricted them to cynomolgus RBCs, demonstrating that this gene is selectively required for parasite multiplication and growth in human RBCs. NBPXa-null parasites could bind to human RBCs, but invasion of these cells was severely impaired. Therefore, NBPXa is identified as a key mediator of P. knowlesi human infection and may be a target for vaccine development against this emerging pathogen.

  12. Maintaining the immunological balance in parasitic infections: a role for TGF-ß?

    Omer, F M; Kurtzhals, J A; Riley, E M

    2000-01-01

    on the one hand and prevention of immune-mediated pathology on the other. In this article, Fakhereldin Omer, Jørgen Kurtzhals and Eleanor Riley review the immunoregulatory properties of TGF-beta in the context of parasitic infections. Data from murine malaria infections suggest that TGF-beta modifies...

  13. Supplementation with Abscisic Acid Reduces Malaria Disease Severity and Parasite Transmission

    Glennon, Elizabeth K. K.; Adams, L. Garry; Hicks, Derrick R.; Dehesh, Katayoon; Luckhart, Shirley

    2016-01-01

    Nearly half of the world's population is at risk for malaria. Increasing drug resistance has intensified the need for novel therapeutics, including treatments with intrinsic transmission-blocking properties. In this study, we demonstrate that the isoprenoid abscisic acid (ABA) modulates signaling in the mammalian host to reduce parasitemia and the formation of transmissible gametocytes and in the mosquito host to reduce parasite infection. Oral ABA supplementation in a mouse model of malaria was well tolerated and led to reduced pathology and enhanced gene expression in the liver and spleen consistent with infection recovery. Oral ABA supplementation also increased mouse plasma ABA to levels that can signal in the mosquito midgut upon blood ingestion. Accordingly, we showed that supplementation of a Plasmodium falciparum-infected blood meal with ABA increased expression of mosquito nitric oxide synthase and reduced infection prevalence in a nitric oxide-dependent manner. Identification of the mechanisms whereby ABA reduces parasite growth in mammals and mosquitoes could shed light on the balance of immunity and metabolism across eukaryotes and provide a strong foundation for clinical translation. PMID:27001761

  14. Apicomplexa-specific tRip facilitates import of exogenous tRNAs into malaria parasites.

    Bour, Tania; Mahmoudi, Nassira; Kapps, Delphine; Thiberge, Sabine; Bargieri, Daniel; Ménard, Robert; Frugier, Magali

    2016-04-26

    The malaria-causing Plasmodium parasites are transmitted to vertebrates by mosquitoes. To support their growth and replication, these intracellular parasites, which belong to the phylum Apicomplexa, have developed mechanisms to exploit their hosts. These mechanisms include expropriation of small metabolites from infected host cells, such as purine nucleotides and amino acids. Heretofore, no evidence suggested that transfer RNAs (tRNAs) could also be exploited. We identified an unusual gene in Apicomplexa with a coding sequence for membrane-docking and structure-specific tRNA binding. This Apicomplexa protein-designated tRip (tRNA import protein)-is anchored to the parasite plasma membrane and directs import of exogenous tRNAs. In the absence of tRip, the fitness of the parasite stage that multiplies in the blood is significantly reduced, indicating that the parasite may need host tRNAs to sustain its own translation and/or as regulatory RNAs. Plasmodium is thus the first example, to our knowledge, of a cell importing exogenous tRNAs, suggesting a remarkable adaptation of this parasite to extend its reach into host cell biology.

  15. Importance of adequate local spatiotemporal transmission measures in malaria cohort studies: application to the relation between placental malaria and first malaria infection in infants.

    Le Port, Agnès; Cottrell, Gilles; Chandre, Fabrice; Cot, Michel; Massougbodji, Achille; Garcia, André

    2013-07-01

    According to several studies, infants whose mothers had a malaria-infected placenta (MIP) at delivery are at increased risk of a first malaria infection. Immune tolerance caused by intrauterine contact with the parasite could explain this phenomenon, but it is also known that infants who are highly exposed to Anopheles mosquitoes infected with Plasmodium are at greater risk of contracting malaria. Consequently, local malaria transmission must be taken into account to demonstrate the immune tolerance hypothesis. From data collected between 2007 and 2010 on 545 infants followed from birth to age 18 months in southern Benin, we compared estimates of the effect of MIP on time to first malaria infection obtained through different Cox models. In these models, MIP was adjusted for either 1) "village-like" time-independent exposure variables or 2) spatiotemporal exposure prediction derived from local climatic, environmental, and behavioral factors. Only the use of exposure prediction improved the model's goodness of fit (Bayesian Information Criterion) and led to clear conclusions regarding the effect of placental infection, whereas the models using the village-like variables were less successful than the univariate model. This demonstrated clearly the benefit of adequately taking transmission into account in cohort studies of malaria.

  16. Generation of genetically attenuated blood-stage malaria parasites; characterizing growth and virulence in a rodent model of malaria

    Lin, Jingwen

    2013-01-01

    Despite intense efforts over the past 50 years to develop a vaccine, there is currently no licensed malaria vaccine available. The limited success in inducing sufficient protection against malaria with subunit-vaccines has renewed an interest in whole-parasite vaccination strategies. While

  17. Emerging Functions of Transcription Factors in Malaria Parasite

    Renu Tuteja

    2011-01-01

    Full Text Available Transcription is a process by which the genetic information stored in DNA is converted into mRNA by enzymes known as RNA polymerase. Bacteria use only one RNA polymerase to transcribe all of its genes while eukaryotes contain three RNA polymerases to transcribe the variety of eukaryotic genes. RNA polymerase also requires other factors/proteins to produce the transcript. These factors generally termed as transcription factors (TFs are either associated directly with RNA polymerase or add in building the actual transcription apparatus. TFs are the most common tools that our cells use to control gene expression. Plasmodium falciparum is responsible for causing the most lethal form of malaria in humans. It shows most of its characteristics common to eukaryotic transcription but it is assumed that mechanisms of transcriptional control in P. falciparum somehow differ from those of other eukaryotes. In this article we describe the studies on the main TFs such as myb protein, high mobility group protein and ApiA2 family proteins from malaria parasite. These studies show that these TFs are slowly emerging to have defined roles in the regulation of gene expression in the parasite.

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

    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

  19. Malaria and helminth co-infections in outpatients of Alaba Kulito Health Center, southern Ethiopia: a cross sectional study

    Legesse Mengistu

    2010-05-01

    Full Text Available Abstract Background Distribution of malaria and intestinal helminths is known to overlap in developing tropical countries of the world. Co-infections with helminth and malaria parasites cause a significant and additive problem against the host. The aim of this study was to asses the prevalence of malaria/helminth co-infection and the associated problems among febrile outpatients that attended Alaba Kulito Health Center, southern Ethiopia November and December 2007. A total of 1802 acute febrile patients were diagnosed for malaria. 458 Giemsa-stained thick and thin blood films were used for identification of Plasmodium species and Stool samples prepared using Kato-Katz technique were used to examine for intestinal helminths. Haemoglobin concentration was measured using a portable spectrophotometer (Hemocue HB 201. Anthropometry-based nutritional assessment of the study participants was done by measuring body weight to the nearest 0.1 kg and height to the nearest 0.1 cm. Findings 458 of the total febrile patients were positive for malaria. Co infection with Plasmodium and helminth parasites is associated with significantly (p Plasmodium parasites. And this difference was also significant for haemoglobin concentration (F = 10.18, p = 0.002, in which patients co infected with Plasmodium and helminth parasites showed lower mean haemoglobin concentration. More than one-third of the infected cases in both malaria infections and malaria/helminth co infections are undernourished. However the statistics for the difference is not significant. Conclusion Malaria and soil-transmitted helminthiasis obviously contribute to anaemia and low weight status and these conditions are more pronounced in individuals concurrently infected with malaria and soil-transmitted helminths. Hence, simultaneous combat against the two parasitic infections is very crucial to improve health of the affected communities.

  20. Malaria parasite carbonic anhydrase: inhibition of aromatic/heterocyclic sulfonamides and its therapeutic potential

    Krungkrai, Sudaratana R; Krungkrai, Jerapan

    2011-01-01

    Plasmodium falciparum (P. falciparum) is responsible for the majority of life-threatening cases of human malaria, causing 1.5-2.7 million annual deaths. The global emergence of drug-resistant malaria parasites necessitates identification and characterization of novel drug targets and their potential inhibitors. We identified the carbonic anhydrase (CA) genes in P. falciparum. The pfCA gene encodes anα-carbonic anhydrase, a Zn2+-metalloenzme, possessing catalytic properties distinct from that of the human host CA enzyme. The amino acid sequence of the pfCA enzyme is different from the analogous protozoan and human enzymes. A library of aromatic/heterocyclic sulfonamides possessing a large diversity of scaffolds were found to be very good inhibitors for the malarial enzyme at moderate-low micromolar and submicromolar inhibitions. The structure of the groups substituting the aromatic-ureido- or aromatic-azomethine fragment of the molecule and the length of the parent sulfonamide were critical parameters for the inhibitory properties of the sulfonamides. One derivative, that is, 4- (3, 4-dichlorophenylureido)thioureido-benzenesulfonamide (compound 10) was the most effective in vitro Plasmodium falciparum CA inhibitor, and was also the most effective antimalarial compound on the in vitro P. falciparum growth inhibition. The compound 10 was also effective in vivo antimalarial agent in mice infected with Plasmodium berghei, an animal model of drug testing for human malaria infection. It is therefore concluded that the sulphonamide inhibitors targeting the parasite CA may have potential for the development of novel therapies against human malaria. PMID:23569766

  1. Proteomic profiling of Plasmodium sporozoite maturation identifies new proteins essential for parasite development and infectivity

    Lasonder, Edwin; Janse, Chris J; van Gemert, Geert-Jan

    2008-01-01

    Plasmodium falciparum sporozoites that develop and mature inside an Anopheles mosquito initiate a malaria infection in humans. Here we report the first proteomic comparison of different parasite stages from the mosquito -- early and late oocysts containing midgut sporozoites, and the mature...... whose annotation suggest an involvement in sporozoite maturation, motility, infection of the human host and associated metabolic adjustments. Analyses of proteins identified in the P. falciparum sporozoite proteomes by orthologous gene disruption in the rodent malaria parasite, P. berghei, revealed...... three previously uncharacterized Plasmodium proteins that appear to be essential for sporozoite development at distinct points of maturation in the mosquito. This study sheds light on the development and maturation of the malaria parasite in an Anopheles mosquito and also identifies proteins that may...

  2. Diversity, loss, and gain of malaria parasites in a globally invasive bird.

    Marzal, Alfonso; Ricklefs, Robert E; Valkiūnas, Gediminas; Albayrak, Tamer; Arriero, Elena; Bonneaud, Camille; Czirják, Gábor A; Ewen, John; Hellgren, Olof; Hořáková, Dita; Iezhova, Tatjana A; Jensen, Henrik; Križanauskienė, Asta; Lima, Marcos R; de Lope, Florentino; Magnussen, Eyðfinn; Martin, Lynn B; Møller, Anders P; Palinauskas, Vaidas; Pap, Péter L; Pérez-Tris, Javier; Sehgal, Ravinder N M; Soler, Manuel; Szöllosi, Eszter; Westerdahl, Helena; Zetindjiev, Pavel; Bensch, Staffan

    2011-01-01

    Invasive species can displace natives, and thus identifying the traits that make aliens successful is crucial for predicting and preventing biodiversity loss. Pathogens may play an important role in the invasive process, facilitating colonization of their hosts in new continents and islands. According to the Novel Weapon Hypothesis, colonizers may out-compete local native species by bringing with them novel pathogens to which native species are not adapted. In contrast, the Enemy Release Hypothesis suggests that flourishing colonizers are successful because they have left their pathogens behind. To assess the role of avian malaria and related haemosporidian parasites in the global spread of a common invasive bird, we examined the prevalence and genetic diversity of haemosporidian parasites (order Haemosporida, genera Plasmodium and Haemoproteus) infecting house sparrows (Passer domesticus). We sampled house sparrows (N = 1820) from 58 locations on 6 continents. All the samples were tested using PCR-based methods; blood films from the PCR-positive birds were examined microscopically to identify parasite species. The results show that haemosporidian parasites in the house sparrows' native range are replaced by species from local host-generalist parasite fauna in the alien environments of North and South America. Furthermore, sparrows in colonized regions displayed a lower diversity and prevalence of parasite infections. Because the house sparrow lost its native parasites when colonizing the American continents, the release from these natural enemies may have facilitated its invasion in the last two centuries. Our findings therefore reject the Novel Weapon Hypothesis and are concordant with the Enemy Release Hypothesis.

  3. Diversity, loss, and gain of malaria parasites in a globally invasive bird.

    Alfonso Marzal

    Full Text Available Invasive species can displace natives, and thus identifying the traits that make aliens successful is crucial for predicting and preventing biodiversity loss. Pathogens may play an important role in the invasive process, facilitating colonization of their hosts in new continents and islands. According to the Novel Weapon Hypothesis, colonizers may out-compete local native species by bringing with them novel pathogens to which native species are not adapted. In contrast, the Enemy Release Hypothesis suggests that flourishing colonizers are successful because they have left their pathogens behind. To assess the role of avian malaria and related haemosporidian parasites in the global spread of a common invasive bird, we examined the prevalence and genetic diversity of haemosporidian parasites (order Haemosporida, genera Plasmodium and Haemoproteus infecting house sparrows (Passer domesticus. We sampled house sparrows (N = 1820 from 58 locations on 6 continents. All the samples were tested using PCR-based methods; blood films from the PCR-positive birds were examined microscopically to identify parasite species. The results show that haemosporidian parasites in the house sparrows' native range are replaced by species from local host-generalist parasite fauna in the alien environments of North and South America. Furthermore, sparrows in colonized regions displayed a lower diversity and prevalence of parasite infections. Because the house sparrow lost its native parasites when colonizing the American continents, the release from these natural enemies may have facilitated its invasion in the last two centuries. Our findings therefore reject the Novel Weapon Hypothesis and are concordant with the Enemy Release Hypothesis.

  4. In-depth comparative analysis of malaria parasite genomes reveals protein-coding genes linked to human disease in Plasmodium falciparum genome.

    Liu, Xuewu; Wang, Yuanyuan; Liang, Jiao; Wang, Luojun; Qin, Na; Zhao, Ya; Zhao, Gang

    2018-05-02

    Plasmodium falciparum is the most virulent malaria parasite capable of parasitizing human erythrocytes. The identification of genes related to this capability can enhance our understanding of the molecular mechanisms underlying human malaria and lead to the development of new therapeutic strategies for malaria control. With the availability of several malaria parasite genome sequences, performing computational analysis is now a practical strategy to identify genes contributing to this disease. Here, we developed and used a virtual genome method to assign 33,314 genes from three human malaria parasites, namely, P. falciparum, P. knowlesi and P. vivax, and three rodent malaria parasites, namely, P. berghei, P. chabaudi and P. yoelii, to 4605 clusters. Each cluster consisted of genes whose protein sequences were significantly similar and was considered as a virtual gene. Comparing the enriched values of all clusters in human malaria parasites with those in rodent malaria parasites revealed 115 P. falciparum genes putatively responsible for parasitizing human erythrocytes. These genes are mainly located in the chromosome internal regions and participate in many biological processes, including membrane protein trafficking and thiamine biosynthesis. Meanwhile, 289 P. berghei genes were included in the rodent parasite-enriched clusters. Most are located in subtelomeric regions and encode erythrocyte surface proteins. Comparing cluster values in P. falciparum with those in P. vivax and P. knowlesi revealed 493 candidate genes linked to virulence. Some of them encode proteins present on the erythrocyte surface and participate in cytoadhesion, virulence factor trafficking, or erythrocyte invasion, but many genes with unknown function were also identified. Cerebral malaria is characterized by accumulation of infected erythrocytes at trophozoite stage in brain microvascular. To discover cerebral malaria-related genes, fast Fourier transformation (FFT) was introduced to extract

  5. A novel ENU-mutation in ankyrin-1 disrupts malaria parasite maturation in red blood cells of mice.

    Andreas Greth

    Full Text Available The blood stage of the plasmodium parasite life cycle is responsible for the clinical symptoms of malaria. Epidemiological studies have identified coincidental malarial endemicity and multiple red blood cell (RBC disorders. Many RBC disorders result from mutations in genes encoding cytoskeletal proteins and these are associated with increased protection against malarial infections. However the mechanisms underpinning these genetic, host responses remain obscure. We have performed an N-ethyl-N-nitrosourea (ENU mutagenesis screen and have identified a novel dominant (haploinsufficient mutation in the Ank-1 gene (Ank1(MRI23420 of mice displaying hereditary spherocytosis (HS. Female mice, heterozygous for the Ank-1 mutation showed increased survival to infection by Plasmodium chabaudi adami DS with a concomitant 30% decrease in parasitemia compared to wild-type, isogenic mice (wt. A comparative in vivo red cell invasion and parasite growth assay showed a RBC-autonomous effect characterised by decreased proportion of infected heterozygous RBCs. Within approximately 6-8 hours post-invasion, TUNEL staining of intraerythrocytic parasites, showed a significant increase in dead parasites in heterozygotes. This was especially notable at the ring and trophozoite stages in the blood of infected heterozygous mutant mice compared to wt (p<0.05. We conclude that increased malaria resistance due to ankyrin-1 deficiency is caused by the intraerythrocytic death of P. chabaudi parasites.

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

    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...... species in which antigenic variation was demonstrated, and it has a close phylogenetic relationship to Plasmodium vivax, the second most important species of human malaria parasite (reviewed in ref. 4). Despite their relatedness, there are important phenotypic differences between them, such as host blood...... cell preference, absence of a dormant liver stage or 'hypnozoite' in P. knowlesi, and length of the asexual cycle (reviewed in ref. 4). Here we present an analysis of the P. knowlesi (H strain, Pk1(A+) clone) nuclear genome sequence. This is the first monkey malaria parasite genome to be described...

  7. Plasmodium falciparum infection in febrile Congolese children: prevalence of clinical malaria 10 years after introduction of artemisinin-combination therapies.

    Etoka-Beka, Mandingha Kosso; Ntoumi, Francine; Kombo, Michael; Deibert, Julia; Poulain, Pierre; Vouvoungui, Christevy; Kobawila, Simon Charles; Koukouikila-Koussounda, Felix

    2016-12-01

    To investigate the proportion of malaria infection in febrile children consulting a paediatric hospital in Brazzaville, to determine the prevalence of submicroscopic malaria infection, to characterise Plasmodium falciparum infection and compare the prevalence of uncomplicated P. falciparum malaria according to haemoglobin profiles. Blood samples were collected from children aged <10 years with an axillary temperature ≥37.5 °C consulting the paediatric ward of Marien Ngouabi Hospital in Brazzaville. Parasite density was determined and all samples were screened for P. falciparum by nested polymerase chain reaction (PCR) using the P. falciparum msp-2 marker to detect submicroscopic infections and characterise P. falciparum infection. Sickle cell trait was screened by PCR. A total of 229 children with fever were recruited, of whom 10% were diagnosed with uncomplicated malaria and 21% with submicroscopic infection. The mean parasite density in children with uncomplicated malaria was 42 824 parasites/μl of blood. The multiplicity of infection (MOI) was 1.59 in children with uncomplicated malaria and 1.69 in children with submicroscopic infection. The mean haemoglobin level was 10.1 ± 1.7 for children with uncomplicated malaria and 12.0 ± 8.6 for children with submicroscopic infection. About 13% of the children harboured the sickle cell trait (HbAS); the rest had normal haemoglobin (HbAA). No difference in prevalence of uncomplicated malaria and submicroscopic infection, parasite density, haemoglobin level, MOI and P. falciparum genetic diversity was observed according to haemoglobin type. The low prevalence of uncomplicated malaria in febrile Congolese children indicates the necessity to investigate carefully other causes of fever. © 2016 John Wiley & Sons Ltd.

  8. Optimized Pan-species and speciation duplex real-time PCR assays for Plasmodium parasites detection in malaria vectors.

    Maurice Marcel Sandeu

    Full Text Available 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, P<0.05. The relative quantification of Plasmodium 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

  9. Prevalence of intestinal parasitic infections among patients ...

    Gastrointestinal helminths and protozoan parasites may cause mild, acute and chronic human infections. There is inadequate reliable information on the epidemiology of these parasites among patients attending tertiary hospitals in Tanzania. This retrospective study was conducted using hospital data obtained from the ...

  10. Using rapid diagnostic tests as source of malaria parasite DNA for molecular analyses in the era of declining malaria prevalence

    Ishengoma, Deus S; Lwitiho, Sudi; Madebe, Rashid A

    2011-01-01

    was conducted to examine if sufficient DNA could be successfully extracted from malaria rapid diagnostic tests (RDTs), used and collected as part of routine case management services in health facilities, and thus forming the basis for molecular analyses, surveillance and quality control (QC) testing of RDTs....... continued molecular surveillance of malaria parasites is important to early identify emerging anti-malarial drug resistance, it is becoming increasingly difficult to obtain parasite samples from ongoing studies, such as routine drug efficacy trials. To explore other sources of parasite DNA, this study...

  11. Malaria infection during pregnancy in area of stable transmission ...

    Malaria infection during pregnancy in area of stable transmission. ... (LBW), a leading cause of neonatal death in areas of stable malaria transmission. ... areas of stable malaria transmission and the effective strategies for prevention and control. Keywords: malaria, pregnancy, semi-immune women, anaemia, low birthweight

  12. The diagnosis of malaria infection using a solid-phase radioimmunoassay for the detection of malaria antigens

    Mackey, L.; Perrin, L.; Leemans, E.; Lambert, P.H.

    1980-01-01

    A method was devised to show that malaria parasites can be detected serologically in infected blood with a high degree of sensitivity. Using a murine malaria model, parasites were demonstrated in a solid-phase radio-immunoassay which measured antibody-binding inhibition. Lysed red blood cells (r.b.c.) were incubated with labelled specific antibody and were then reacted in antigen-coated tubes. The degree of inhibition of antibody binding in the tubes correlated with the level of parasitaemia in the test blood. Using homologous antisera the test detected infection at a level of 1 parasite/million r.b.c.. The specificity of the method was shown by comparison of antibody-binding inhibition in normal and infected r.b.c. and in r.b.c. from non-infected mice with induced reticulocytosis. The sensitivity was shown in vitro in tests of serially diluted blood of high parasitaemia and in vivo for the detection of early infection. The presence of antibody in the test blood did not significantly affect the sensitivity of parasite detection. (author)

  13. Asymptomatic falciparum malaria and intestinal helminths co-infection among school children in Osogbo, Nigeria

    Olusola Ojurongbe

    2011-01-01

    Full Text Available Background: Malaria and intestinal helminths are parasitic diseases causing high morbidity and mortality in most tropical parts of the world, where climatic conditions and sanitation practices favor their prevalence. The aim of this study was to determine the prevalence and possible impact of falciparum malaria and intestinal helminths co-infection among school children in Kajola, Osun state, Nigeria. Methods: Fresh stool and blood samples were collected from 117 primary school children age range 4-15 years. The stool samples were processed using both Kato-Katz and formol-ether concentration techniques and microscopically examined for intestinal parasitic infections. Blood was collected by finger prick to determine malaria parasitemia using thick film method; and packed cell volume (PCV was determined by hematocrit. Univariate analysis and chi-square statistical tests were used to analyze the data. Results: The prevalence of Plasmodium falciparum, intestinal helminth infections, and co-infection of malaria and helminth in the study were 25.6%, 40.2% and 4.3%, respectively. Five species of intestinal helminths were recovered from the stool samples and these were Ascaris lumbricoides (34.2%, hookworm (5.1%, Trichuris trichiura (2.6%, Diphyllobothrium latum (0.9% and Trichostrongylus species (0.9%. For the co-infection of both malaria and intestinal helminths, females (5.9% were more infected than males (2.0% but the difference was not statistically significant (p = 0.3978. Children who were infected with helminths were equally likely to be infected with malaria as children without intestinal helminths [Risk Ratio (RR = 0.7295]. Children with A. lumbricoides (RR = 1.359 were also likely to be infected with P. falciparum as compared with uninfected children. Conclusions: Asymptomatic falciparum malaria and intestinal helminth infections do co-exist without clinical symp-toms in school children in Nigeria.

  14. [Malaria and HIV infection: clinical and biological aspects at Donka National Hospital in Conakry, Guinea].

    Bald, I; Camara, A; Baldé, O; Magassouba, N F; Bah, M S; Makanéra, A; Gamy, E P

    2010-08-01

    Malaria and HIV/AIDS are two of the most widespread infectious diseases encountered in sub-Saharan Africa. Even minor interactions between these two diseases could have substantial effects on public health. The purpose of this study was to investigate associations between malaria and HIV infection. Study was carried out over an 8-month period (April 1, 2003 to November 30, 2003) in the Tropical and Infectious Diseases Department of the Donka National Hospital in Conakry, Guinea. A total of 89 malaria patients including 41 cases with HIV infection and 48 controls without HIV infection were included. All patients were hospitalized during the study and provided informed consent. Results showed that malaria affected all age groups in the same proportion. Mean patient age was 34 years (range, 15 and 76 years). Males were more frequently infected with a sex ratio of 1.05. The average number of malaria episodes was higher in cases (malaria with HIV-infection than in controls (malaria without HIV infection). Hyperthermia was observed in most cases (68.29%) and controls (77.08%). Severe anemia was observed in 26.82% of cases versus 10.41% of controls. Low parasite density was observed in 73.17% of cases as compared to 68.75% of controls. The recovery rate was higher in the control group than in case group: 27.08% versus 14.63%. The death rate was higher in the case group than in the control group: 21.95% versus 6.25%. These findings demonstrate a link between malaria and HIV. The frequency of malaria episodes was higher in patients with HIV infection than patients without HIV infection and the outcome of malarial episodes was better in patients without HIV infection.

  15. Parasite density and the spectrum of clinical illness in falciparum malaria

    Ali, H.; Mahmood, T.; Ahmed, N.

    2008-01-01

    To determine the impact of percentage parasitemia and clinical features on morbidity and mortality in patients with P. falciparum malaria. Seventy-six adult patients of smear positive P. falciparum malaria were selected for the study. Parasite density was estimated on thin blood film and expressed as percentage of red blood cells parasitized. Patients were divided into three groups on the basis of parasite density. The data was analyzed on SPSS version 12. Results were expressed as percentages, mean and standard deviations. P-value 10%. Comparative analysis of the groups showed that pallor, impaired consciousness, jaundice or malarial hepatitis, thrombocytopenia, acute renal failure, DIC, and mortality were all strongly associated with the density of Plasmodium falciparum malaria (p=0.001). Parasite density was not related to age, gender and hepatosplenomegaly. High parasite density was associated with severe clinical illness, complications and mortality. Parasite counts of > 5% may be considered as hyperparasitaemia in this population of the world. (author)

  16. Malaria infectivity of xanthurenic acid-deficient anopheline mosquitoes produced by TALEN-mediated targeted mutagenesis.

    Yamamoto, Daisuke S; Sumitani, Megumi; Hatakeyama, Masatsugu; Matsuoka, Hiroyuki

    2018-02-01

    Anopheline mosquitoes are major vectors of malaria parasites. When the gametocytes of the malaria parasite are transferred from a vertebrate to mosquitoes, they differentiate into gametes, and are fertilized in the midguts of mosquitoes. Xanthurenic acid (XA), a waste product of the ommochrome synthesis pathway, has been shown to induce exflagellation during microgametogenesis in vitro; however, it currently remains unclear whether endogenous XA affects the infectivity of anopheline mosquitoes to malaria parasites in vivo due to the lack of appropriate experimental systems such as a XA-deficient line. In the present study, we produced a XA-deficient line in Anopheles stephensi using transcription activator-like effector nuclease (TALEN)-mediated gene targeting (knockout) of the kynurenine 3-monooxygenase (kmo) gene, which encodes an enzyme that participates in the ommochrome synthesis pathway. The knockout of kmo resulted in the absence of XA, and oocyst formation was inhibited in the midguts of these XA-deficient mosquitoes, which, in turn, reduced sporozoite numbers in their salivary glands. These results suggest that endogenous XA stimulates exflagellation, and enhances the infectivity of anopheline mosquitoes to malaria parasites in vivo. The XA-deficient line of the anopheline mosquito provides a useful system for analyzing and understanding the associated factors of malaria gametogenesis in the mosquito midgut.

  17. Malaria, Epstein-Barr virus infection and the pathogenesis of Burkitt's lymphoma.

    Mawson, Anthony R; Majumdar, Suvankar

    2017-11-01

    A geographical and causal connection has long been recognized between malaria, Epstein-Barr virus (EBV) infection and Burkitt's lymphoma (BL), but the underlying mechanisms remain obscure. Potential clues are that the malaria parasite Plasmodium falciparum selectively absorbs vitamin A from the host and depends on it for its biological activities; secondly, alterations in vitamin A (retinoid) metabolism have been implicated in many forms of cancer, including BL. The first author has proposed that the merozoite-stage malaria parasite, emerging from the liver, uses its absorbed vitamin A as a cell membrane destabilizer to invade the red blood cells, causing anemia and other signs and symptoms of the disease as manifestations of an endogenous form of hypervitaminosis A (Mawson AR, Path Global Health 2013;107(3):122-9). Repeated episodes of malaria would therefore be expected to expose the tissues of affected individuals to potentially toxic doses of vitamin A. It is proposed that such episodes activate latent EBV infection, which in turn activates retinoid-responsive genes. Expression of these genes enhances viral replication and induces germinal center (GC) B cell expansion, activation-induced cytidine deaminase (AID) expression, and c-myc translocation, which in turn predisposes to BL. Thus, an endogenous form of retinoid toxicity related to malaria infection may be the common factor linking frequent malaria, EBV infection and BL, whereby prolonged exposure of lymphatic tissues to high concentrations of retinoids may combine to induce B-cell translocation and increase the risk of Burkitt's lymphoma. © 2017 UICC.

  18. A subset of group A-like var genes encodes the malaria parasite ligands for binding to human brain endothelial cells

    Claessens, Antoine; Adams, Yvonne; Ghumra, Ashfaq

    2012-01-01

    Cerebral malaria is the most deadly manifestation of infection with Plasmodium falciparum. The pathology of cerebral malaria is characterized by the accumulation of infected erythrocytes (IEs) in the microvasculature of the brain caused by parasite adhesins on the surface of IEs binding to human...... receptors on microvascular endothelial cells. The parasite and host molecules involved in this interaction are unknown. We selected three P. falciparum strains (HB3, 3D7, and IT/FCR3) for binding to a human brain endothelial cell line (HBEC-5i). The whole transcriptome of isogenic pairs of selected.......029) but not by antibodies from controls with uncomplicated malaria (Mann-Whitney test, P = 0.58). This work describes a binding phenotype for virulence-associated group A P. falciparum erythrocyte membrane protein 1 variants and identifies targets for interventions to treat or prevent cerebral malaria....

  19. Proteomic profiling of Plasmodium sporozoite maturation identifies new proteins essential for parasite development and infectivity.

    Lasonder, E.; Janse, C.J.; Gemert, G.J.A. van; Mair, G.R.; Vermunt, A.M.W.; Douradinha, B.G.; Noort, V. van; Huynen, M.A.; Luty, A.J.F.; Kroeze, H.; Khan, S.M.; Sauerwein, R.W.; Waters, A.P.; Mann, M.; Stunnenberg, H.G.

    2008-01-01

    Plasmodium falciparum sporozoites that develop and mature inside an Anopheles mosquito initiate a malaria infection in humans. Here we report the first proteomic comparison of different parasite stages from the mosquito -- early and late oocysts containing midgut sporozoites, and the mature,

  20. Enlightening the malaria parasite life cycle: bioluminescent Plasmodium in fundamental and applied research

    Giulia eSiciliano

    2015-05-01

    Full Text Available The unicellular protozoan parasites of the genus Plasmodium impose on human health worldwide the enormous burden of malaria. The possibility to genetically modify several species of malaria parasites represented a major advance in the possibility to elucidate their biology and is now turning laboratory lines of transgenic Plasmodium into precious weapons to fight malaria. Amongst the various genetically modified plasmodia, transgenic parasite lines expressing bioluminescent reporters have been essential to unveil mechanisms of parasite gene expression and to develop in vivo imaging approaches in mouse malaria models. Mainly the human malaria parasite Plasmodium falciparum and the rodent parasite Plasmodium berghei have been engineered to express bioluminescent reporters in almost all the developmental stages of the parasite along its complex life cycle between the insect and the vertebrate hosts. Plasmodium lines expressing conventional and improved luciferase reporters are now gaining a central role to develop cell based assays in the much needed search of new antimalarial drugs and to open innovative approaches for both fundamental and applied research in malaria.

  1. Enlightening the malaria parasite life cycle: bioluminescent Plasmodium in fundamental and applied research.

    Siciliano, Giulia; Alano, Pietro

    2015-01-01

    The unicellular protozoan parasites of the genus Plasmodium impose on human health worldwide the enormous burden of malaria. The possibility to genetically modify several species of malaria parasites represented a major advance in the possibility to elucidate their biology and is now turning laboratory lines of transgenic Plasmodium into precious weapons to fight malaria. Amongst the various genetically modified plasmodia, transgenic parasite lines expressing bioluminescent reporters have been essential to unveil mechanisms of parasite gene expression and to develop in vivo imaging approaches in mouse malaria models. Mainly the human malaria parasite Plasmodium falciparum and the rodent parasite P. berghei have been engineered to express bioluminescent reporters in almost all the developmental stages of the parasite along its complex life cycle between the insect and the vertebrate hosts. Plasmodium lines expressing conventional and improved luciferase reporters are now gaining a central role to develop cell based assays in the much needed search of new antimalarial drugs and to open innovative approaches for both fundamental and applied research in malaria.

  2. Recognition of Human Erythrocyte Receptors by the Tryptophan-Rich Antigens of Monkey Malaria Parasite Plasmodium knowlesi.

    Kriti Tyagi

    Full Text Available The monkey malaria parasite Plasmodium knowlesi also infect humans. There is a lack of information on the molecular mechanisms that take place between this simian parasite and its heterologous human host erythrocytes leading to this zoonotic disease. Therefore, we investigated here the binding ability of P. knowlesi tryptophan-rich antigens (PkTRAgs to the human erythrocytes and sharing of the erythrocyte receptors between them as well as with other commonly occurring human malaria parasites.Six PkTRAgs were cloned and expressed in E.coli as well as in mammalian CHO-K1 cell to determine their human erythrocyte binding activity by cell-ELISA, and in-vitro rosetting assay, respectively.Three of six PkTRAgs (PkTRAg38.3, PkTRAg40.1, and PkTRAg67.1 showed binding to human erythrocytes. Two of them (PkTRAg40.1 and PkTRAg38.3 showed cross-competition with each other as well as with the previously described P.vivax tryptophan-rich antigens (PvTRAgs for human erythrocyte receptors. However, the third protein (PkTRAg67.1 utilized the additional but different human erythrocyte receptor(s as it did not cross-compete for erythrocyte binding with either of these two PkTRAgs as well as with any of the PvTRAgs. These three PkTRAgs also inhibited the P.falciparum parasite growth in in-vitro culture, further indicating the sharing of human erythrocyte receptors by these parasite species and the biological significance of this receptor-ligand interaction between heterologous host and simian parasite.Recognition and sharing of human erythrocyte receptor(s by PkTRAgs with human parasite ligands could be part of the strategy adopted by the monkey malaria parasite to establish inside the heterologous human host.

  3. Recognition of Human Erythrocyte Receptors by the Tryptophan-Rich Antigens of Monkey Malaria Parasite Plasmodium knowlesi.

    Tyagi, Kriti; Gupta, Deepali; Saini, Ekta; Choudhary, Shilpa; Jamwal, Abhishek; Alam, Mohd Shoeb; Zeeshan, Mohammad; Tyagi, Rupesh K; Sharma, Yagya D

    2015-01-01

    The monkey malaria parasite Plasmodium knowlesi also infect humans. There is a lack of information on the molecular mechanisms that take place between this simian parasite and its heterologous human host erythrocytes leading to this zoonotic disease. Therefore, we investigated here the binding ability of P. knowlesi tryptophan-rich antigens (PkTRAgs) to the human erythrocytes and sharing of the erythrocyte receptors between them as well as with other commonly occurring human malaria parasites. Six PkTRAgs were cloned and expressed in E.coli as well as in mammalian CHO-K1 cell to determine their human erythrocyte binding activity by cell-ELISA, and in-vitro rosetting assay, respectively. Three of six PkTRAgs (PkTRAg38.3, PkTRAg40.1, and PkTRAg67.1) showed binding to human erythrocytes. Two of them (PkTRAg40.1 and PkTRAg38.3) showed cross-competition with each other as well as with the previously described P.vivax tryptophan-rich antigens (PvTRAgs) for human erythrocyte receptors. However, the third protein (PkTRAg67.1) utilized the additional but different human erythrocyte receptor(s) as it did not cross-compete for erythrocyte binding with either of these two PkTRAgs as well as with any of the PvTRAgs. These three PkTRAgs also inhibited the P.falciparum parasite growth in in-vitro culture, further indicating the sharing of human erythrocyte receptors by these parasite species and the biological significance of this receptor-ligand interaction between heterologous host and simian parasite. Recognition and sharing of human erythrocyte receptor(s) by PkTRAgs with human parasite ligands could be part of the strategy adopted by the monkey malaria parasite to establish inside the heterologous human host.

  4. Incidence of human malaria infection in central areas of balochistan: mastung and khuzdar

    Yasinzai, M.I.; Kakarsulemankhet, J.K.

    2007-01-01

    To determine the incidence of malarial parasites in human population of Mastung and Khuzdar areas of Pakistan. Malarial parasites were identified in the blood slides of suspected patients of the disease from July, 2004 to June, 2006 in 7852 subjects. Out of 7852 suspected cases of malaria, 2092 (26.64 %) were found to be positive for malarial parasite. In Mastung, out of 3644 suspected cases, 896 (24.58 %) were found to be positive for malarial parasites with 52.67 % (472/896) identified as P. vivax and 47.32 % (424/ 896) as P. falciparum infection. The highest rate of infections (73.13 %) was recorded in August while lowest rate of infection (24.27%) was noted in October. In Khuzdar, out of 4208 suspected cases, 1196 (28.42 %) were found to be positive for malarial parasites with 69.89 % (836/1196) identified as P. vivax. and 30.10 % (360/1196) as P. falciparum infection. The highest rate of infections (84.84%) was recorded in December while the lowest rate of infection (56.06%) was noted in October. There was no case of Plasmodium malaria and P. ovale infection observed in the present study. An over all prevalence rate of 62.52 % of P. vivax was seen. There is no association between types of infection and age of subjects. This high prevalence pose a serious public health threat. (author)

  5. Functional profiles of orphan membrane transporters in the life cycle of the malaria parasite

    Kenthirapalan, S.; Waters, A.P.; Matuschewski, K.; Kooij, T.W.A.

    2016-01-01

    Assigning function to orphan membrane transport proteins and prioritizing candidates for detailed biochemical characterization remain fundamental challenges and are particularly important for medically relevant pathogens, such as malaria parasites. Here we present a comprehensive genetic analysis of

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

    Ramaprasad, Abhinay; Pain, Arnab; Ravasi, Timothy

    2012-01-01

    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

  7. Parasite threshold associated with clinical malaria in areas of different transmission intensities in north eastern Tanzania

    Mmbando, Bruno P; Lusingu, John P; Vestergaard, Lasse S

    2009-01-01

    BACKGROUND: In Sub-Sahara Africa, malaria due to Plasmodium falciparum is the main cause of ill health. Evaluation of malaria interventions, such as drugs and vaccines depends on clinical definition of the disease, which is still a challenge due to lack of distinct malaria specific clinical...... features. Parasite threshold is used in definition of clinical malaria in evaluation of interventions. This however, is likely to be influenced by other factors such as transmission intensity as well as individual level of immunity against malaria. METHODS: This paper describes step function and dose...... response model with threshold parameter as a tool for estimation of parasite threshold for onset of malaria fever in highlands (low transmission) and lowlands (high transmission intensity) strata. These models were fitted using logistic regression stratified by strata and age groups (0-1, 2-3, 4-5, 6...

  8. Prospective identification of malaria parasite genes under balancing selection.

    Kevin K A Tetteh

    Full Text Available Endemic human pathogens are subject to strong immune selection, and interrogation of pathogen genome variation for signatures of balancing selection can identify important target antigens. Several major antigen genes in the malaria parasite Plasmodium falciparum have shown such signatures in polymorphism-versus-divergence indices (comparing with the chimpanzee parasite P. reichenowi, and in allele frequency based indices.To compare methods for prospective identification of genes under balancing selection, 26 additional genes known or predicted to encode surface-exposed proteins of the invasive blood stage merozoite were first sequenced from a panel of 14 independent P. falciparum cultured lines and P. reichenowi. Six genes at the positive extremes of one or both of the Hudson-Kreitman-Aguade (HKA and McDonald-Kreitman (MK indices were identified. Allele frequency based analysis was then performed on a Gambian P. falciparum population sample for these six genes and three others as controls. Tajima's D (TjD index was most highly positive for the msp3/6-like PF10_0348 (TjD = 1.96 as well as the positive control ama1 antigen gene (TjD = 1.22. Across the genes there was a strong correlation between population TjD values and the relative HKA indices (whether derived from the population or the panel of cultured laboratory isolates, but no correlation with the MK indices.Although few individual parasite genes show significant evidence of balancing selection, analysis of population genomic and comparative sequence data with the HKA and TjD indices should discriminate those that do, and thereby identify likely targets of immunity.

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

    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. PMID:27022937

  10. Increased eosinophil activity in acute Plasmodium falciparum infection - association with cerebral malaria

    Kurtzhals, J A; Reimert, C M; Tette, E

    1998-01-01

    To assess the eosinophil response to Plasmodium falciparum infection a cohort of initially parasite-free Ghanaian children was followed for 3 months. Seven of nine children who acquired an asymptomatic P. falciparum infection showed increase in eosinophil counts, while a decrease was found in seven...... of nine children with symptomatic malaria, and no change was observed in 14 children who remained parasite-free. In a hospital-based study, paediatric patients with cerebral malaria (CM), severe anaemia (SA), or uncomplicated malaria (UM) had uniformly low eosinophil counts during the acute illness...... followed by eosinophilia 30 days after cure. Plasma levels of eosinophil cationic protein (ECP) and eosinophil protein X (EPX) were measured as indicators of eosinophil activation. In spite of the low eosinophil counts, ECP levels were increased on day 0 and significantly higher in patients with CM...

  11. An essential malaria protein defines the architecture of blood-stage and transmission-stage parasites.

    Absalon, Sabrina; Robbins, Jonathan A; Dvorin, Jeffrey D

    2016-04-28

    Blood-stage replication of the human malaria parasite Plasmodium falciparum occurs via schizogony, wherein daughter parasites are formed by a specialized cytokinesis known as segmentation. Here we identify a parasite protein, which we name P. falciparum Merozoite Organizing Protein (PfMOP), as essential for cytokinesis of blood-stage parasites. We show that, following PfMOP knockdown, parasites undergo incomplete segmentation resulting in a residual agglomerate of partially divided cells. While organelles develop normally, the structural scaffold of daughter parasites, the inner membrane complex (IMC), fails to form in this agglomerate causing flawed segmentation. In PfMOP-deficient gametocytes, the IMC formation defect causes maturation arrest with aberrant morphology and death. Our results provide insight into the mechanisms of replication and maturation of malaria parasites.

  12. Molecular architecture of a complex between an adhesion protein from the malaria parasite and intracellular adhesion molecule 1

    Brown, Alan; Turner, Louise; Christoffersen, Stig

    2013-01-01

    The adhesion of Plasmodium falciparum-infected erythrocytes to human tissues or endothelium is central to the pathology caused by the parasite during malaria. It contributes to the avoidance of parasite clearance by the spleen and to the specific pathologies of cerebral and placental malaria....... The PfEMP1 family of adhesive proteins is responsible for this sequestration by mediating interactions with diverse human ligands. In addition, as the primary targets of acquired, protective immunity, the PfEMP1s are potential vaccine candidates. PfEMP1s contain large extracellular ectodomains made from......, intercellular adhesion molecule-1 (ICAM-1). We show through small angle x-ray scattering that IT4VAR13 is rigid, elongated, and monomeric. We also show that it interacts with ICAM-1 through the DBLß domain alone, forming a 1:1 complex. These studies provide a first low resolution structural view of a PfEMP1...

  13. Mechanisms of stage-transcending protection following immunization of mice with late liver stage-arresting genetically attenuated malaria parasites.

    Brandon K Sack

    2015-05-01

    Full Text Available Malaria, caused by Plasmodium parasite infection, continues to be one of the leading causes of worldwide morbidity and mortality. Development of an effective vaccine has been encumbered by the complex life cycle of the parasite that has distinct pre-erythrocytic and erythrocytic stages of infection in the mammalian host. Historically, malaria vaccine development efforts have targeted each stage in isolation. An ideal vaccine, however, would target multiple life cycle stages with multiple arms of the immune system and be capable of eliminating initial infection in the liver, the subsequent blood stage infection, and would prevent further parasite transmission. We have previously shown that immunization of mice with Plasmodium yoelii genetically attenuated parasites (GAP that arrest late in liver stage development elicits stage-transcending protection against both a sporozoite challenge and a direct blood stage challenge. Here, we show that this immunization strategy engenders both T- and B-cell responses that are essential for stage-transcending protection, but the relative importance of each is determined by the host genetic background. Furthermore, potent anti-blood stage antibodies elicited after GAP immunization rely heavily on FC-mediated functions including complement fixation and FC receptor binding. These protective antibodies recognize the merozoite surface but do not appear to recognize the immunodominant merozoite surface protein-1. The antigen(s targeted by stage-transcending immunity are present in both the late liver stages and blood stage parasites. The data clearly show that GAP-engendered protective immune responses can target shared antigens of pre-erythrocytic and erythrocytic parasite life cycle stages. As such, this model constitutes a powerful tool to identify novel, protective and stage-transcending T and B cell targets for incorporation into a multi-stage subunit vaccine.

  14. Spleen-dependent regulation of antigenic variation in malaria parasites: Plasmodium knowlesi SICAvar expression profiles in splenic and asplenic hosts.

    Stacey A Lapp

    Full Text Available Antigenic variation by malaria parasites was first described in Plasmodium knowlesi, which infects humans and macaque monkeys, and subsequently in P. falciparum, the most virulent human parasite. The schizont-infected cell agglutination (SICA variant proteins encoded by the SICAvar multigene family in P. knowlesi, and Erythrocyte Membrane Protein-1 (EMP-1 antigens encoded by the var multigene family in P. falciparum, are expressed at the surface of infected erythrocytes, are associated with virulence, and serve as determinants of naturally acquired immunity. A parental P. knowlesi clone, Pk1(A+, and a related progeny clone, Pk1(B+1+, derived by an in vivo induced variant antigen switch, were defined by the expression of distinct SICA variant protein doublets of 210/190 and 205/200 kDa, respectively. Passage of SICA[+] infected erythrocytes through splenectomized rhesus monkeys results in the SICA[-] phenotype, defined by the lack of surface expression and agglutination with variant specific antisera.We have investigated SICAvar RNA and protein expression in Pk1(A+, Pk1(B+1+, and SICA[-] parasites. The Pk1(A+ and Pk1(B+1+ parasites express different distinct SICAvar transcript and protein repertoires. By comparison, SICA[-] parasites are characterized by a vast reduction in SICAvar RNA expression, the lack of full-length SICAvar transcript signals on northern blots, and correspondingly, the absence of any SICA protein detected by mass spectrometry.SICA protein expression may be under transcriptional as well as post-transcriptional control, and we show for the first time that the spleen, an organ central to blood-stage immunity in malaria, exerts an influence on these processes. Furthermore, proteomics has enabled the first in-depth characterization of SICA[+] protein phenotypes and we show that the in vivo switch from Pk1(A+ to Pk1(B+1+ parasites resulted in a complete change in SICA profiles. These results emphasize the importance of studying

  15. Exo-erythrocytic development of avian malaria and related haemosporidian parasites.

    Valkiūnas, Gediminas; Iezhova, Tatjana A

    2017-03-03

    Avian malaria parasites (Plasmodium spp.) and related haemosporidians (Haemosporida) are responsible for diseases which can be severe and even lethal in avian hosts. These parasites cause not only blood pathology, but also damage various organs due to extensive exo-erythrocytic development all over the body, which is not the case during Plasmodium infections in mammals. However, exo-erythrocytic development (tissue merogony or schizogony) remains the most poorly investigated part of life cycle in all groups of wildlife haemosporidian parasites. In spite of remarkable progress in studies of genetic diversity, ecology and evolutionary biology of avian haemosporidians during the past 20 years, there is not much progress in understanding patterns of exo-erythrocytic development in these parasites. The purpose of this review is to overview the main information on exo-erythrocytic development of avian Plasmodium species and related haemosporidian parasites as a baseline for assisting academic and veterinary medicine researchers in morphological identification of these parasites using tissue stages, and to define future research priorities in this field of avian malariology. The data were considered from peer-reviewed articles and histological material that was accessed in zoological collections in museums of Australia, Europe and the USA. Articles describing tissue stages of avian haemosporidians were included from 1908 to the present. Histological preparations of various organs infected with the exo-erythrocytic stages of different haemosporidian parasites were examined. In all, 229 published articles were included in this review. Exo-erythrocytic stages of avian Plasmodium, Fallisia, Haemoproteus, Leucocytozoon, and Akiba species were analysed, compared and illustrated. Morphological characters of tissue stages that can be used for diagnostic purposes were specified. Recent molecular studies combined with histological research show that avian haemosporidians are more

  16. Lineage-specific positive selection at the merozoite surface protein 1 (msp1 locus of Plasmodium vivax and related simian malaria parasites

    Kawai Satoru

    2010-02-01

    Full Text Available Abstract Background The 200 kDa merozoite surface protein 1 (MSP-1 of malaria parasites, a strong vaccine candidate, plays a key role during erythrocyte invasion and is a target of host protective immune response. Plasmodium vivax, the most widespread human malaria parasite, is closely related to parasites that infect Asian Old World monkeys, and has been considered to have become a parasite of man by host switch from a macaque malaria parasite. Several Asian monkey parasites have a range of natural hosts. The same parasite species shows different disease manifestations among host species. This suggests that host immune responses to P. vivax-related malaria parasites greatly differ among host species (albeit other factors. It is thus tempting to invoke that a major immune target parasite protein such as MSP-1 underwent unique evolution, depending on parasite species that exhibit difference in host range and host specificity. Results We performed comparative phylogenetic and population genetic analyses of the gene encoding MSP-1 (msp1 from P. vivax and nine P. vivax-related simian malaria parasites. The inferred phylogenetic tree of msp1 significantly differed from that of the mitochondrial genome, with a striking displacement of P. vivax from a position close to P. cynomolgi in the mitochondrial genome tree to an outlier of Asian monkey parasites. Importantly, positive selection was inferred for two ancestral branches, one leading to P. inui and P. hylobati and the other leading to P. vivax, P. fieldi and P. cynomolgi. This ancestral positive selection was estimated to have occurred three to six million years ago, coinciding with the period of radiation of Asian macaques. Comparisons of msp1 polymorphisms between P. vivax, P. inui and P. cynomolgi revealed that while some positively selected amino acid sites or regions are shared by these parasites, amino acid changes greatly differ, suggesting that diversifying selection is acting species

  17. A central role for P48/45 in malaria parasite male gamete fertility.

    Dijk, M.R. van; Janse, C.J.; Thompson, J.; Waters, A.P.; Braks, J.A.M.; Dodemont, H.J.; Stunnenberg, H.G.; Gemert, G.J.A. van; Sauerwein, R.W.; Eling, W.M.C.

    2001-01-01

    Fertilization and zygote development are obligate features of the malaria parasite life cycle and occur during parasite transmission to mosquitoes. The surface protein PFS48/45 is expressed by male and female gametes of Plasmodium falciparum and PFS48/45 antibodies prevent zygote development and

  18. Methodology and application of flow cytometry for investigation of human malaria parasites.

    Grimberg, Brian T

    2011-03-31

    Historically, examinations of the inhibition of malaria parasite growth/invasion, whether using drugs or antibodies, have relied on the use of microscopy or radioactive hypoxanthine uptake. These are considered gold standards for measuring the effectiveness of antimalarial treatments, however, these methods have well known shortcomings. With the advent of flow cytometry coupled with the use of fluorescent DNA stains allowed for increased speed, reproducibility, and qualitative estimates of the effectiveness of antibodies and drugs to limit malaria parasite growth which addresses the challenges of traditional techniques. Because materials and machines available to research facilities are so varied, different methods have been developed to investigate malaria parasites by flow cytometry. This review is intended to serve as a reference guide for advanced users and importantly, as a primer for new users, to support expanded use and improvements to malaria flow cytometry, particularly in endemic countries. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. The Host Genetic Diversity in Malaria Infection

    Vitor R. R. de Mendonça

    2012-01-01

    Full Text Available Populations exposed to Plasmodium infection develop genetic mechanisms of protection against severe disease. The clinical manifestation of malaria results primarily from the lysis of infected erythrocytes and subsequent immune and inflammatory responses. Herein, we review the genetic alterations associated with erythrocytes or mediators of the immune system, which might influence malaria outcome. Moreover, polymorphisms in genes related to molecules involved in mechanisms of cytoadherence and their influence on malaria pathology are also discussed. The results of some studies have suggested that the combinatorial effects of a set of genetic factors in the erythrocyte-immunology pathway might be relevant to host resistance or susceptibility against Plasmodium infection. However, these results must be interpreted with caution because of the differences observed in the functionality and frequency of polymorphisms within different populations. With the recent advances in molecular biology techniques, more robust studies with reliable data have been reported, and the results of these studies have identified individual genetic factors for consideration in preventing severe disease and the individual response to treatment.

  20. NSR-seq transcriptional profiling enables identification of a gene signature of Plasmodium falciparum parasites infecting children

    Vignali, Marissa; Armour, Christopher D.; Chen, Jingyang; Morrison, Robert; Castle, John C.; Biery, Matthew C.; Bouzek, Heather; Moon, Wonjong; Babak, Tomas; Fried, Michal; Raymond, Christopher K.; Duffy, Patrick E.

    2011-01-01

    Malaria caused by Plasmodium falciparum results in approximately 1 million annual deaths worldwide, with young children and pregnant mothers at highest risk. Disease severity might be related to parasite virulence factors, but expression profiling studies of parasites to test this hypothesis have been hindered by extensive sequence variation in putative virulence genes and a preponderance of host RNA in clinical samples. We report here the application of RNA sequencing to clinical isolates of P. falciparum, using not-so-random (NSR) primers to successfully exclude human ribosomal RNA and globin transcripts and enrich for parasite transcripts. Using NSR-seq, we confirmed earlier microarray studies showing upregulation of a distinct subset of genes in parasites infecting pregnant women, including that encoding the well-established pregnancy malaria vaccine candidate var2csa. We also describe a subset of parasite transcripts that distinguished parasites infecting children from those infecting pregnant women and confirmed this observation using quantitative real-time PCR and mass spectrometry proteomic analyses. Based on their putative functional properties, we propose that these proteins could have a role in childhood malaria pathogenesis. Our study provides proof of principle that NSR-seq represents an approach that can be used to study clinical isolates of parasites causing severe malaria syndromes as well other blood-borne pathogens and blood-related diseases. PMID:21317536

  1. NSR-seq transcriptional profiling enables identification of a gene signature of Plasmodium falciparum parasites infecting children.

    Vignali, Marissa; Armour, Christopher D; Chen, Jingyang; Morrison, Robert; Castle, John C; Biery, Matthew C; Bouzek, Heather; Moon, Wonjong; Babak, Tomas; Fried, Michal; Raymond, Christopher K; Duffy, Patrick E

    2011-03-01

    Malaria caused by Plasmodium falciparum results in approximately 1 million annual deaths worldwide, with young children and pregnant mothers at highest risk. Disease severity might be related to parasite virulence factors, but expression profiling studies of parasites to test this hypothesis have been hindered by extensive sequence variation in putative virulence genes and a preponderance of host RNA in clinical samples. We report here the application of RNA sequencing to clinical isolates of P. falciparum, using not-so-random (NSR) primers to successfully exclude human ribosomal RNA and globin transcripts and enrich for parasite transcripts. Using NSR-seq, we confirmed earlier microarray studies showing upregulation of a distinct subset of genes in parasites infecting pregnant women, including that encoding the well-established pregnancy malaria vaccine candidate var2csa. We also describe a subset of parasite transcripts that distinguished parasites infecting children from those infecting pregnant women and confirmed this observation using quantitative real-time PCR and mass spectrometry proteomic analyses. Based on their putative functional properties, we propose that these proteins could have a role in childhood malaria pathogenesis. Our study provides proof of principle that NSR-seq represents an approach that can be used to study clinical isolates of parasites causing severe malaria syndromes as well other blood-borne pathogens and blood-related diseases.

  2. Plasmodial Hsp70s are functionally adapted to the malaria parasite life cycle

    Jude M Przyborski

    2015-06-01

    Full Text Available The human malaria parasite, Plasmodium falciparum, encodes a minimal complement of six heat shock protein 70s (PfHSP70s, some of which are highly expressed and are thought to play an important role in the survival and pathology of the parasite. In addition to canonical features of molecular chaperones, these HSP70s possess properties that reflect functional adaptation to a parasitic life style, including resistance to thermal insult during fever periods and host-parasite interactions. The parasite even exports an HSP70 to the host cell where it is likely to be involved in host cell modification. This review focuses on the features of the PfHSP70s, particularly with respect to their adaptation to the malaria parasite life cycle.

  3. Prevalence of malaria infection in Butajira area, south-central Ethiopia

    Woyessa Adugna

    2012-03-01

    Full Text Available Abstract Background In 2005, the Ethiopian government launched a massive expansion of the malaria prevention and control programme. The programme was aimed mainly at the reduction of malaria in populations living below 2,000 m above sea level. Global warming has been implicated in the increase in the prevalence of malaria in the highlands. However, there is still a paucity of information on the occurrence of malaria at higher altitudes. The objective of this study was to estimate malaria prevalence in highland areas of south-central Ethiopia, designated as the Butajira area. Methods Using a multi-stage sampling technique, 750 households were selected. All consenting family members were examined for malaria parasites in thick and thin blood smears. The assessment was repeated six times for two years (October 2008 to June 2010. Results In total, 19,207 persons were examined in the six surveys. From those tested, 178 slides were positive for malaria, of which 154 (86.5% were positive for Plasmodium vivax and 22 (12.4% for Plasmodium falciparum; the remaining two (1.1% showed mixed infections of Plasmodium falciparum and Plasmodium vivax. The incidence of malaria was higher after the main rainy season, both in lower lying and in highland areas. The incidence in the highlands was low and similar for all age groups, whereas in the lowlands, malaria occurred mostly in those of one to nine years of age. Conclusion This study documented a low prevalence of malaria that varied with season and altitudinal zone in a highland-fringe area of Ethiopia. Most of the malaria infections were attributable to Plasmodium vivax.

  4. Cytokine expression in malaria-infected non-human primate placentas

    M.M. Gicheru

    2012-06-01

    Full Text Available Malaria parasites are known to mediate the induction of inflammatory immune responses at the maternal-foetal interface during placental malaria (PM leading to adverse consequences like pre-term deliveries and abortions. Immunological events that take place within the malaria-infected placental micro-environment leading to retarded foetal growth and disruption of pregnancies are among the critical parameters that are still in need of further elucidation. The establishment of more animal models for studying placental malaria can provide novel ways of circumventing problems experienced during placental malaria research in humans such as inaccurate estimation of gestational ages. Using the newly established olive baboon (Papio anubis-Plasmodium knowlesi (P. knowlesi H strain model of placental malaria, experiments were carried out to determine placental cytokine profiles underlying the immunopathogenesis of placental malaria. Four pregnant olive baboons were infected with blood stage P. knowlesi H strain parasites on the one fiftieth day of gestation while four other uninfected pregnant olive baboons were maintained as uninfected controls. After nine days of infection, placentas were extracted from all the eight baboons through cesarean surgery and used for the processing of placental plasma and sera samples for cytokine sandwich enzyme linked immunosorbent assays (ELISA. Results indicated that the occurrence of placental malaria was associated with elevated concentrations of tumour necrosis factor alpha (TNF-α and interleukin 12 (IL-12. Increased levels of IL-4, IL-6 and IL-10 and interferon gamma (IFN-γ levels were detected in uninfected placentas. These findings match previous reports regarding immunity during PM thereby demonstrating the reliability of the olive baboon-P. knowlesi model for use in further studies.

  5. Knowledge based assessment of intestinal parasitic Infections ...

    There is an apparent lack of information on the risk and clinical symptoms of Intestinal Parasitic Infections (IPIs) among students attending boarding secondary schools in Ebonyi State, Nigeria. This questionnaire-based survey attempts to assess some behavioural habits, possible risk factor(s) as well as clinical symptoms ...

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

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

    2007-01-01

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

  7. Labelling malaria-infected human erythrocytes with Tc-99m

    Garmelius-Larsson, B.; Pettersson, F.; Vogt, A.; Jonsson, C.

    2002-01-01

    Aim: Malaria is an old and a very common disease, especially in undeveloped countries. The malaria parasites infect the erythrocytes and the aim of this work was to label infected cells for future studies of their distribution and life span. Material and Method: With a commercial kit containing stannous fluoride and sodium medronate, which is used to label erythrocytes in vivo, in vitro and in vivo/vitro methods, we labelled the cells by using a modified method and a small volume, 5 - 50 microlitre, of packed cells. The cells were labelled with Tc-99m in the range of 60 - 1500 MBq. The kit was reconstituted with saline and the pH was adjusted to 7.0. The cells were incubated with 1 ml of the kitsolution in 37 0 C for 5 min. The remaining Sn-ions were reduced by adding NaOCl and then the solution was centrifuged.The supernantant was discarded and the Tc-99m was added to the precipitate and incubated 37 0 C for 20 min and then washed 3 times. This labelling procedure was performed on both infected and on non-infected cells. Results: Ten samples of cells have been labelled. The best labelling result was obtained using 7 - 20 MBq per 10 microlitre of packed cells. The labelling efficiency was, on average, 35%. Conclusion: It is possible to label both infected and non-infected cells in very small volumes. The cells were visually inspected in a microscope and were viable after labelling. Furthermore, the cell distribution was traced in vivo in an animal model by a gamma camera

  8. Recent Advances of Malaria Parasites Detection Systems Based on Mathematical Morphology

    Andrea Loddo

    2018-02-01

    Full Text Available Malaria is an epidemic health disease and a rapid, accurate diagnosis is necessary for proper intervention. Generally, pathologists visually examine blood stained slides for malaria diagnosis. Nevertheless, this kind of visual inspection is subjective, error-prone and time-consuming. In order to overcome the issues, numerous methods of automatic malaria diagnosis have been proposed so far. In particular, many researchers have used mathematical morphology as a powerful tool for computer aided malaria detection and classification. Mathematical morphology is not only a theory for the analysis of spatial structures, but also a very powerful technique widely used for image processing purposes and employed successfully in biomedical image analysis, especially in preprocessing and segmentation tasks. Microscopic image analysis and particularly malaria detection and classification can greatly benefit from the use of morphological operators. The aim of this paper is to present a review of recent mathematical morphology based methods for malaria parasite detection and identification in stained blood smears images.

  9. Recent Advances of Malaria Parasites Detection Systems Based on Mathematical Morphology.

    Loddo, Andrea; Di Ruberto, Cecilia; Kocher, Michel

    2018-02-08

    Malaria is an epidemic health disease and a rapid, accurate diagnosis is necessary for proper intervention. Generally, pathologists visually examine blood stained slides for malaria diagnosis. Nevertheless, this kind of visual inspection is subjective, error-prone and time-consuming. In order to overcome the issues, numerous methods of automatic malaria diagnosis have been proposed so far. In particular, many researchers have used mathematical morphology as a powerful tool for computer aided malaria detection and classification. Mathematical morphology is not only a theory for the analysis of spatial structures, but also a very powerful technique widely used for image processing purposes and employed successfully in biomedical image analysis, especially in preprocessing and segmentation tasks. Microscopic image analysis and particularly malaria detection and classification can greatly benefit from the use of morphological operators. The aim of this paper is to present a review of recent mathematical morphology based methods for malaria parasite detection and identification in stained blood smears images.

  10. Placental Histopathologic Changes Associated with Subclinical Malaria Infection and Its Impact on the Fetal Environment

    Parekh, Falgunee K.; Davison, Billie B.; Gamboa, Dionicia; Hernandez, Jean; Branch, OraLee H.

    2010-01-01

    Microscopic examination of placental tissue can provide an accurate assessment of malaria infection during pregnancy. In this cross-sectional study of 193 women in Iquitos, Peru, 1.0% and 6.6% had parasites in the peripheral blood as detected by microscopy and polymerase chain reaction, respectively. However, 22% had placental malaria pigment indicating past, subclinical infections. Placental tissues with pigment from 24 cases were matched by gravidity and month of delivery to 24 controls and histopathologically examined. Cases had significantly higher number of monocytes in the intervillous space (44.7 versus 25.5; P = 0.012). Pigmented monocytes in fetal vessels were present in 33.3% of cases. This study demonstrated that subclinical malarial infection occurred frequently in pregnant women and is associated with increased presence of monocytes in the placenta. Pigmented monocytes in fetal vessels suggest parasites can breach the placental barrier and enter the fetal circulation. PMID:21036823

  11. Probability of Transmission of Malaria from Mosquito to Human Is Regulated by Mosquito Parasite Density in Naïve and Vaccinated Hosts.

    Thomas S Churcher

    2017-01-01

    Full Text Available Over a century since Ronald Ross discovered that malaria is caused by the bite of an infectious mosquito it is still unclear how the number of parasites injected influences disease transmission. Currently it is assumed that all mosquitoes with salivary gland sporozoites are equally infectious irrespective of the number of parasites they harbour, though this has never been rigorously tested. Here we analyse >1000 experimental infections of humans and mice and demonstrate a dose-dependency for probability of infection and the length of the host pre-patent period. Mosquitoes with a higher numbers of sporozoites in their salivary glands following blood-feeding are more likely to have caused infection (and have done so quicker than mosquitoes with fewer parasites. A similar dose response for the probability of infection was seen for humans given a pre-erythrocytic vaccine candidate targeting circumsporozoite protein (CSP, and in mice with and without transfusion of anti-CSP antibodies. These interventions prevented infection more efficiently from bites made by mosquitoes with fewer parasites. The importance of parasite number has widespread implications across malariology, ranging from our basic understanding of the parasite, how vaccines are evaluated and the way in which transmission should be measured in the field. It also provides direct evidence for why the only registered malaria vaccine RTS,S was partially effective in recent clinical trials.

  12. Aspidosperma (Apocynaceae plant cytotoxicity and activity towards malaria parasites. Part I: Aspidosperma nitidum (Benth used as a remedy to treat fever and malaria in the Amazon

    Julia Penna Coutinho

    2013-12-01

    Full Text Available Infusions of Aspidosperma nitidum (Apocynaceae wood bark are used to treat fever and malaria in the Amazon Region. Several species of this family are known to possess indole alkaloids and other classes of secondary metabolites, whereas terpenoids, an inositol and the indole alkaloids harmane-3 acid and braznitidumine have been described in A. nitidum . In the present study, extracts from the wood bark, leaves and branches of this species were prepared for assays against malaria parasites and cytotoxicity testing using human hepatoma and normal monkey kidney cells. The wood bark extracts were active against Plasmodium falciparum and showed a low cytotoxicity in vitro, whereas the leaf and branch extracts and the pure alkaloid braznitidumine were inactive. A crude methanol extract was subjected to acid-base fractionation aimed at obtaining alkaloid-rich fractions, which were active at low concentrations against P. falciparum and in mice infected with and sensitive Plasmodium berghei parasites. Our data validate the antimalarial usefulness of A. nitidum wood bark, a remedy that can most likely help to control malaria. However, the molecules responsible for this antimalarial activity have not yet been identified. Considering their high selectivity index, the alkaloid-rich fractions from the plant bark might be useful in the development of new antimalarials.

  13. Complete avian malaria parasite genomes reveal features associated with lineage-specific evolution in birds and mammals

    Böhme, Ulrike; Otto, Thomas D.; Cotton, James A.; Steinbiss, Sascha; Sanders, Mandy; Oyola, Samuel O.; Nicot, Antoine; Gandon, Sylvain; Patra, Kailash P.; Herd, Colin; Bushell, Ellen; Modrzynska, Katarzyna K.; Billker, Oliver; Vinetz, Joseph M.; Rivero, Ana; Newbold, Chris I.; Berriman, Matthew

    2018-01-01

    Avian malaria parasites are prevalent around the world and infect a wide diversity of bird species. Here, we report the sequencing and analysis of high-quality draft genome sequences for two avian malaria species, Plasmodium relictum and Plasmodium gallinaceum. We identify 50 genes that are specific to avian malaria, located in an otherwise conserved core of the genome that shares gene synteny with all other sequenced malaria genomes. Phylogenetic analysis suggests that the avian malaria species form an outgroup to the mammalian Plasmodium species, and using amino acid divergence between species, we estimate the avian- and mammalian-infective lineages diverged in the order of 10 million years ago. Consistent with their phylogenetic position, we identify orthologs of genes that had previously appeared to be restricted to the clades of parasites containing Plasmodium falciparum and Plasmodium vivax, the species with the greatest impact on human health. From these orthologs, we explore differential diversifying selection across the genus and show that the avian lineage is remarkable in the extent to which invasion-related genes are evolving. The subtelomeres of the P. relictum and P. gallinaceum genomes contain several novel gene families, including an expanded surf multigene family. We also identify an expansion of reticulocyte binding protein homologs in P. relictum, and within these proteins, we detect distinct regions that are specific to nonhuman primate, humans, rodent, and avian hosts. For the first time in the Plasmodium lineage, we find evidence of transposable elements, including several hundred fragments of LTR-retrotransposons in both species and an apparently complete LTR-retrotransposon in the genome of P. gallinaceum. PMID:29500236

  14. Probing the cytoadherence of malaria infected red blood cells under flow.

    Xiaofeng Xu

    Full Text Available Malaria is one of the most widespread and deadly human parasitic diseases caused by the Plasmodium (P. species with the P. falciparum being the most deadly. The parasites are capable of invading red blood cells (RBCs during infection. At the late stage of parasites' development, the parasites export proteins to the infected RBCs (iRBC membrane and bind to receptors of surface proteins on the endothelial cells that line microvasculature walls. Resulting adhesion of iRBCs to microvasculature is one of the main sources of most complications during malaria infection. Therefore, it is important to develop a versatile and simple experimental method to quantitatively investigate iRBCs cytoadhesion and binding kinetics. Here, we developed an advanced flow based adhesion assay to demonstrate that iRBC's adhesion to endothelial CD36 receptor protein coated channels is a bistable process possessing a hysteresis loop. This finding confirms a recently developed model of cell adhesion which we used to fit our experimental data. We measured the contact area of iRBC under shear flow at different stages of infection using Total Internal Reflection Fluorescence (TIRF, and also adhesion receptor and ligand binding kinetics using Atomic Force Microscopy (AFM. With these parameters, we reproduced in our model the experimentally observed changes in adhesion properties of iRBCs accompanying parasite maturation and investigated the main mechanisms responsible for these changes, which are the contact area during the shear flow as well as the rupture area size.

  15. Diverse sampling of East African haemosporidians reveals chiropteran origin of malaria parasites in primates and rodents.

    Lutz, Holly L; Patterson, Bruce D; Kerbis Peterhans, Julian C; Stanley, William T; Webala, Paul W; Gnoske, Thomas P; Hackett, Shannon J; Stanhope, Michael J

    2016-06-01

    Phylogenies of parasites provide hypotheses on the history of their movements between hosts, leading to important insights regarding the processes of host switching that underlie modern-day epidemics. Haemosporidian (malaria) parasites lack a well resolved phylogeny, which has impeded the study of evolutionary processes associated with host-switching in this group. Here we present a novel phylogenetic hypothesis that suggests bats served as the ancestral hosts of malaria parasites in primates and rodents. Expanding upon current taxon sampling of Afrotropical bat and bird parasites, we find strong support for all major nodes in the haemosporidian tree using both Bayesian and maximum likelihood approaches. Our analyses support a single transition of haemosporidian parasites from saurian to chiropteran hosts, and do not support a monophyletic relationship between Plasmodium parasites of birds and mammals. We find, for the first time, that Hepatocystis and Plasmodium parasites of mammals represent reciprocally monophyletic evolutionary lineages. These results highlight the importance of broad taxonomic sampling when analyzing phylogenetic relationships, and have important implications for our understanding of key host switching events in the history of malaria parasite evolution. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. MALARIA AND HIV IN ADULTS: When The Parasite runs into The Virus

    Emanuele Focà

    2012-01-01

    Full Text Available

    Malaria and HIV/AIDS are among the principal causes of morbidity and mortality worldwide, particularly in resource-limited settings such as sub-Saharan Africa. Despite the international community’s efforts to reduce incidence and prevalence of these diseases, they remain a global public health problem. Clinical manifestations of malaria may be more severe in HIV infected patients, which have higher risks of severe malaria and malaria related death. Co-infected pregnant women, children and international travelers from non-malaria endemic countries are at higher risk of clinical complications. However, there is a paucity and conflicting data regarding malaria and HIV co-infection, particularly on how HIV infection can modify the response to antimalarial drugs and about drug-interactions between antiretroviral agents and artemisinin-based combined regimens. Moreover, consulting HIV-infected international travelers and physicians specialized in HIV care and travel medicine should prescribe an adequate chemoprophylaxis in patients travelling towards malaria endemic areas and pay attention on interactions between antiretrovirals and antimalarial prophylaxis drugs in order to prevent clinical complications of this co-infection.

    This review aims to evaluate the available international literature on malaria and HIV co-infection in adults providing a critical comprehensive review of nowadays knowledge.

  17. MALARIA AND HIV IN ADULTS: When The Parasite runs into The Virus

    Emanuele Focà

    2012-05-01

    Full Text Available Malaria and HIV/AIDS are among the principal causes of morbidity and mortality worldwide, particularly in resource-limited settings such as sub-Saharan Africa. Despite the international community’s efforts to reduce incidence and prevalence of these diseases, they remain a global public health problem. Clinical manifestations of malaria may be more severe in HIV infected patients, which have higher risks of severe malaria and malaria related death. Co-infected pregnant women, children and international travelers from non-malaria endemic countries are at higher risk of clinical complications. However, there is a paucity and conflicting data regarding malaria and HIV co-infection, particularly on how HIV infection can modify the response to antimalarial drugs and about drug-interactions between antiretroviral agents and artemisinin-based combined regimens. Moreover, consulting HIV-infected international travelers and physicians specialized in HIV care and travel medicine should prescribe an adequate chemoprophylaxis in patients travelling towards malaria endemic areas and pay attention on interactions between antiretrovirals and antimalarial prophylaxis drugs in order to prevent clinical complications of this co-infection. This review aims to evaluate the available international literature on malaria and HIV co-infection in adults providing a critical comprehensive review of nowadays knowledge.

  18. Atypical lymphocytes in malaria mimicking dengue infection in Thailand

    Polrat Wilairatana

    2010-09-01

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

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

    Abkallo, Hussein M.

    2017-07-13

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

  20. Prevalence of human malaria infection in Pakistani areas bordering with Iran

    Yasinzai, M. I.; Kakarsulemankhel, J. K.

    2013-01-01

    Objective: To study the prevalence of malarial infections in human population of district Panjgur in south-western Pakistan. Methods: The cross-sectional study identified malarial parasites in the blood slides of 6119 suspected malaria patients from July 2006 to June 2008 through passive and active case detection methods. SPSS 11 was used for statistical analysis. Results: Out of 6119 suspected cases of malaria, 2346 (38.3%) were found to be positive for malarial parasite on blood smear slides. Of these, 1868 (79.6%) cases were due to Plasmodium vivax infection, and 478 (20.3%) had P. falciparum. However, seasonal variation was also noted: P. vivax infection was the highest (n=131/144, 90.9%) in November and the lowest (n=83/176, 47.1%) in October. The prevalence was higher (n=1831, 78%) in males. Age-wise, the prevalence of the disease was 81.2% (n=334) and 80% (n=860) for age groups 1-10 years and 11-20 years. No case of P. malaria and P. ovale was detected in the study period. No association was found between types of infection and age groups. Conclusion: Human malaria infection was quite frequent in the study region, which is one of the hottest areas of Balochistan, Pakistan. In clinically-suspected cases of malaria, there was a high slide positivity rate. The high prevalence rate of P. vivax poses a significant health hazard but P. falciparum also may lead to serious complications, including cerebral malaria. (author)

  1. Presence of IgE cells in human placenta is independent of malaria infection or chorioamnionitis

    Rindsjö, E; Hulthén Varli, I; Ofori, M F

    2006-01-01

    We have shown previously that numerous IgE(+) macrophage-like cells are present in the villous stroma of full term placenta and that there was no difference in the amount of IgE(+) cells between allergic and non-allergic mothers. The presence of such an abundant number of IgE(+) cells...... from Ghana with and without malaria parasites. The immunohistochemical staining pattern for IgE looked similar to our previous study, with the IgE located on Hofbauer-like cells. We could not find any difference in the amount or distribution of IgE(+) cells between malaria-infected and non...

  2. Intestinal parasitic infection among school children.

    Shakya, B; Shrestha, S; Madhikarmi, N L; Adhikari, R

    2012-01-01

    Intestinal parasitosis is a major public health problem of developing countries, children being major victims. Higher prevalence has been reported among school children, mostly in hilly regions of Nepal. This study aims at assessing prevalence of intestinal parasitosis among school children of a school in a border town of Nepal and the associated factors. Fecal samples from the students were examined by direct smear technique and result was correlated with their socioeconomic status and hygienic behavior. The chi-square test was used for analytical assessment. The prevalence rate was 13.9%, girls being highly infected (19.1%) than boys (10.3%) (P>0.05). Entamoeba histolytica (36.0%) was the commonest parasite followed by A. lumbricoides (28.0%). The highest positive rate was found among children of 5 years and less age (29.2%) and least among those above 12 years (5.3%) (P>0.05). Those from family size 5 and less than 5 were least infected (10.5%). Children of illiterate parents (16.7%) and farmers (17.1%) were more infected than literate ones and non-farmers (P>0.05). 8.7% of positive children had multi-parasitic infection. Children drinking untreated water (15.0%) were more infected than those drinking treated water (5.5%) (P>0.05). Intestinal parasitic infection was found among 17% school children. Awareness on infectious diseases, improving hygiene, and application of supportive programs for parents to elevate socioeconomic conditions may reduce the burden of infection.

  3. EU grid computing effort takes on malaria

    Lawrence, Stacy

    2006-01-01

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

  4. Current and cumulative malaria infections in a setting embarking on elimination: Amhara, Ethiopia.

    Yalew, Woyneshet G; Pal, Sampa; Bansil, Pooja; Dabbs, Rebecca; Tetteh, Kevin; Guinovart, Caterina; Kalnoky, Michael; Serda, Belendia A; Tesfay, Berhane H; Beyene, Belay B; Seneviratne, Catherine; Littrell, Megan; Yokobe, Lindsay; Noland, Gregory S; Domingo, Gonzalo J; Getachew, Asefaw; Drakeley, Chris; Steketee, Richard W

    2017-06-08

    Since 2005, Ethiopia has aggressively scaled up malaria prevention and case management. As a result, the number of malaria cases and deaths has significantly declined. In order to track progress towards the elimination of malaria in Amhara Region, coverage of malaria control tools and current malaria transmission need to be documented. A cross-sectional household survey oversampling children under 5 years of age was conducted during the dry season in 2013. A bivalent rapid diagnostic test (RDT) detecting both Plasmodium falciparum and Plasmodium vivax and serology assays using merozoite antigens from both these species were used to assess the prevalence of malaria infections and exposure to malaria parasites in 16 woredas (districts) in Amhara Region. 7878 participants were included, with a mean age of 16.8 years (range 0.5-102.8 years) and 42.0% being children under 5 years of age. The age-adjusted RDT-positivity for P. falciparum and P. vivax infection was 1.5 and 0.4%, respectively, of which 0.05% presented as co-infections. Overall age-adjusted seroprevalence was 30.0% for P. falciparum, 21.8% for P. vivax, and seroprevalence for any malaria species was 39.4%. The prevalence of RDT-positive infections varied by woreda, ranging from 0.0 to 8.3% and by altitude with rates of 3.2, 0.7, and 0.4% at under 2000, 2000-2500, and >2500 m, respectively. Serological analysis showed heterogeneity in transmission intensity by area and altitude and evidence for a change in the force of infection in the mid-2000s. Current and historic malaria transmission across Amhara Region show substantial variation by age and altitude with some settings showing very low or near-zero transmission. Plasmodium vivax infections appear to be lower but relatively more stable across geography and altitude, while P. falciparum is the dominant infection in the higher transmission, low-altitude areas. Age-dependent seroprevalence analyses indicates a drop in transmission occurred in the mid

  5. Bacteraemia, urinary tract infection and malaria in hospitalised ...

    . However, it remains unclear whether such infections are attributable to the malaria, other risk factors, or are coincidental. Objective: To determine the prevalence of bacteraemia and urinary tract infections (UTI) in febrile hospitalised children ...

  6. Communal prevalence of malaria parasite and evaluation of Long ...

    This study investigates the prevalence of malaria and evaluates Long Lasting Insecticide Nets (LLINs) utilization for malaria control in Ikenne LGA, Ogun State, Nigeria. A cross-sectional survey was conducted in five major communities in Ikenne Local Government Area (LGA) namely: Ilisan, Ikenne, Iperu, Ogere and Irolu.

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

    Read Andrew F

    2009-04-01

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

  8. Parasitic infections and maternal anaemia among expectant mothers in the Dangme East District of Ghana.

    Tay, Samuel Crowther Kofi; Nani, Emmanuel Agbeko; Walana, Williams

    2017-01-03

    Parasitic infections are of public health concern globally, particular among at risk groups such as pregnant women in developing countries. The presence of these parasites during pregnancy potentiate adverse effects to both the mother and the unborn baby. This study sought to establish the prevalence of some parasitic agents among antenatal attendees in the Dangme East District of Ghana. A cross-sectional prospective study was conduct between April and July, 2012. Venous blood specimens were collected from each participant for haemoglobin estimation and malaria microscopy. In addition participants' early morning mid-stream urine and stool specimens were analyzed microscopically for parasitic agents. A total of 375 pregnant women were involved in the study, of which anaemia was present in 66.4% (249/375). However, parasitic infections associated anaemia prevalence was 49.6% (186/375). In all, 186 cases of parasitic infections were observed; 171 (44.0%) were single isolated infections while 15 (4.0%) were co-infections. Plasmodium species were significantly associated with anaemia (13.3%, χ 2  = 23.290, p anaemia in pregnancy. Except where co-infections exist (3.7%, χ 2  = 11.267, p = 0.001), the rest of the single infections were insignificantly associated with anaemia. Collectively, intestinal helminthes were predominantly significant with anaemia in pregnancy (p = 0.001, χ 2  = 107.800). The study revealed relatively high prevalence of parasitic infections among the study population, suggesting that about three-quarters of the anaemic mothers are either single or co-infected with parasitic agents.

  9. Toward forward genetic screens in malaria-causing parasites using the piggyBac transposon

    de Koning-Ward Tania F

    2011-03-01

    Full Text Available Abstract The ability to analyze gene function in malaria-causing Plasmodium parasites has received a boost with a recent paper in BMC Genomics that describes a genome-wide mutagenesis system in the rodent malaria species Plasmodium berghei using the transposon piggyBac. This advance holds promise for identifying and validating new targets for intervention against malaria. But further improvements are still needed for the full power of genome-wide molecular genetic screens to be utilized in this organism. See research article: http://www.biomedcentral.com/1471-2164/12/155

  10. Prevalence and associated determinants of malaria parasites among Kenyan children.

    Sultana, Marufa; Sheikh, Nurnabi; Mahumud, Rashidul Alam; Jahir, Tania; Islam, Ziaul; Sarker, Abdur Razzaque

    2017-01-01

    Approximately 80% of deaths attributed to malaria worldwide occurred mainly in Africa in 2015. Kenya is one of the major malaria endemic countries, making malaria the leading public health concern in this country. This study intended to document the prevalence of malaria and determine associated factors including socioeconomic status among children aged 6 months to 14 years in Kenya. This study analyzed the secondary data extracted from the 2015 Kenya Malaria Indicator Survey (KMIS), a cross-sectional country representative survey. Associations of demographic, socioeconomic, community-based, and behavioral factors with the prevalence of malaria in children were analyzed using multivariable logistic regression analysis. Data from 7040 children aged 6 months to 14 years were analyzed. The prevalence of malaria showed an upward trend in terms of age, with the highest prevalence among children aged 11-14 years. Prevalence was also higher among rural children (10.16%) compared to urban children (2.93%), as well as poor children (11.05%) compared to rich children (3.23%). The likelihood of having malaria was higher among children aged 10-14 years (AOR = 4.47, 95% CI = 3.33, 6.02; P level of the household head (AOR = 1.15, 95% CI = 1.08, 2.25; P knowledge in practice to control the malaria burden in Kenya. Furthermore, this study suggests that improving the information available through the mass media and introducing behavior change communication and intervention program specifically for those of poor socioeconomic status will help to reduce malaria cases.

  11. Successful human infection with P. falciparum using three aseptic Anopheles stephensi mosquitoes: a new model for controlled human malaria infection.

    Matthew B Laurens

    Full Text Available Controlled human malaria infection (CHMI is a powerful method for assessing the efficacy of anti-malaria vaccines and drugs targeting pre-erythrocytic and erythrocytic stages of the parasite. CHMI has heretofore required the bites of 5 Plasmodium falciparum (Pf sporozoite (SPZ-infected mosquitoes to reliably induce Pf malaria. We reported that CHMI using the bites of 3 PfSPZ-infected mosquitoes reared aseptically in compliance with current good manufacturing practices (cGMP was successful in 6 participants. Here, we report results from a subsequent CHMI study using 3 PfSPZ-infected mosquitoes reared aseptically to validate the initial clinical trial. We also compare results of safety, tolerability, and transmission dynamics in participants undergoing CHMI using 3 PfSPZ-infected mosquitoes reared aseptically to published studies of CHMI using 5 mosquitoes. Nineteen adults aged 18-40 years were bitten by 3 Anopheles stephensi mosquitoes infected with the chloroquine-sensitive NF54 strain of Pf. All 19 participants developed malaria (100%; 12 of 19 (63% on Day 11. The mean pre-patent period was 258.3 hours (range 210.5-333.8. The geometric mean parasitemia at first diagnosis by microscopy was 9.5 parasites/µL (range 2-44. Quantitative polymerase chain reaction (qPCR detected parasites an average of 79.8 hours (range 43.8-116.7 before microscopy. The mosquitoes had a geometric mean of 37,894 PfSPZ/mosquito (range 3,500-152,200. Exposure to the bites of 3 aseptically-raised, PfSPZ-infected mosquitoes is a safe, effective procedure for CHMI in malaria-naïve adults. The aseptic model should be considered as a new standard for CHMI trials in non-endemic areas. Microscopy is the gold standard used for the diagnosis of Pf malaria after CHMI, but qPCR identifies parasites earlier. If qPCR continues to be shown to be highly specific, and can be made to be practical, rapid, and standardized, it should be considered as an alternative for diagnosis

  12. Gastrointestinal parasite infection of the Gray mouse lemur ...

    Faecal material from 169 individuals of Microcebus murinus living in five littoral forest fragments was analyzed for gastrointestinal parasites. The fragments differed in size and forest quality. Gastrointestinal parasite infection of M. murinus was characterised using parasite species richness, the prevalence of parasites, and ...

  13. Virulence of a malaria parasite, Plasmodium mexicanum, for its sand fly vectors, Lutzomyia vexator and Lutzomyia stewarti (Diptera: Psychodidae).

    Schall, Jos J

    2011-11-01

    Evolutionary theory predicts that virulence of parasites for mobile vector insects will be low for natural parasite-host associations that have coevolved. I determined virulence of the malaria parasite of lizards, Plasmodium mexicanum, for its vectors, two species of sand fly (Diptera: Psychodidae), Lutzomyia vexator (Coquillett 1907) and Lutzomyia stewarti (Mangabeira Fo & Galindo 1944), by measuring several life history traits. Developmental rate from egg to eclosion differed for the two species when noninfected. For both sand fly species, developmental rate for each stage (egg to larval hatching, larval period, pupal period) and life span were not altered by infection. Infected sand flies, however, produced fewer eggs. This reduction in fecundity may be a result of lower quality of the blood meal taken from infected lizards (lower concentration of hemoglobin). This report is the first measure of virulence of Plasmodium for an insect vector other than a mosquito and concords with both expectations of theory and previous studies on natural parasite-host associations that revealed low virulence.

  14. Parasite infection is associated with Kaposi's sarcoma associated herpesvirus (KSHV in Ugandan women

    Ndibazza Juliet

    2011-09-01

    Full Text Available Abstract Background Immune modulation by parasites may influence susceptibility to bacteria and viruses. We examined the association between current parasite infections, HIV and syphilis (measured in blood or stool samples using standard methods and antibodies against Kaposi's sarcoma herpesvirus (KSHV, measured by ELISA, in 1915 stored plasma samples from pregnant women in Entebbe, Uganda. Results Seroprevalence of KSHV was higher in women with malaria parasitaemia (73% vs 60% p = 0.01, hookworm (67% vs 56% p = 0.001 and Mansonella perstans (69% vs 59% p = 0.05; seroprevalence increased with increasing intensity of hookworm infection (p Conclusions Specific parasite infections are associated with presence of antibodies against KSHV, perhaps mediated via their effect on immune function.

  15. Comparison of allele frequencies of Plasmodium falciparum merozoite antigens in malaria infections sampled in different years in a Kenyan population.

    Ochola-Oyier, Lynette Isabella; Okombo, John; Wagatua, Njoroge; Ochieng, Jacob; Tetteh, Kevin K; Fegan, Greg; Bejon, Philip; Marsh, Kevin

    2016-05-06

    Plasmodium falciparum merozoite antigens elicit antibody responses in malaria-endemic populations, some of which are clinically protective, which is one of the reasons why merozoite antigens are the focus of malaria vaccine development efforts. Polymorphisms in several merozoite antigen-encoding genes are thought to arise as a result of selection by the human immune system. The allele frequency distribution of 15 merozoite antigens over a two-year period, 2007 and 2008, was examined in parasites obtained from children with uncomplicated malaria. In the same population, allele frequency changes pre- and post-anti-malarial treatment were also examined. Any gene which showed a significant shift in allele frequencies was also assessed longitudinally in asymptomatic and complicated malaria infections. Fluctuating allele frequencies were identified in codons 147 and 148 of reticulocyte-binding homologue (Rh) 5, with a shift from HD to YH haplotypes over the two-year period in uncomplicated malaria infections. However, in both the asymptomatic and complicated malaria infections YH was the dominant and stable haplotype over the two-year and ten-year periods, respectively. A logistic regression analysis of all three malaria infection populations between 2007 and 2009 revealed, that the chance of being infected with the HD haplotype decreased with time from 2007 to 2009 and increased in the uncomplicated and asymptomatic infections. Rh5 codons 147 and 148 showed heterogeneity at both an individual and population level and may be under some degree of immune selection.

  16. Malaria parasite carriage and risk determinants in a rural population: a malariometric survey in Rwanda

    Kateera, Fredrick; Mens, Petra F.; Hakizimana, Emmanuel; Ingabire, Chantal M.; Muragijemariya, Liberata; Karinda, Parfait; Grobusch, Martin P.; Mutesa, Leon; van Vugt, Michèle

    2015-01-01

    Based on routine health facility case data, Rwanda has achieved a significant malaria burden reduction in the past ten years. However, community-based malaria parasitaemia burden and reasons for continued residual infections, despite a high coverage of control interventions, have yet to be

  17. Liver function assessment in malaria, typhoid and malaria-typhoid co-infection in Aba, Abia State, Nigeria.

    Enemchukwu, B N; Ibe, C C; Udedi, S C; Iroha, A; Ubaoji, K I; Ogundapo, S S

    2014-06-01

    Malaria and typhoid fever are among the most endemic diseases in the tropics and are associated with poverty and underdevelopment with significant morbidity and mortality. Both diseases can lead to liver damage if not properly treated. The liver function assessment was therefore conducted on (90) volunteer patients; comprising (30) patients with malaria only, (30) with typhoid only and (30) with malaria-typhoid co-infection randomly selected from Abia State University Teaching Hospital, Aba, Abia State, Nigeria and (20) healthy individuals were used as control. Blood samples collected from these subjects were screened for malaria parasite and Staphylococcus typhi using standard methods. Mean serum levels of ALP (112.55±84.23), AST (31.33±12.80), ALT (23.10±11.84), TB (19.43±5.02), CB (5.91±3.03) and ALP (116.69±48.68), AST (28.33±11.72), ALT (22.8±5.94), TB (19.31±5.84),CB (5.60±2.50) were obtained for those subjects with malaria and typhoid respectively and subjects with malaria-typhoid co-infection recorded the following; ALP (134.33±56.62), AST (33.97±8.43), ALT (24.40±4.37),TB (21.27±2.96),CB (6.58±3.10) while the control subjects had mean serum levels ofALP (71.05±18.18), AST (16.65±7.45), ALT (13.85±6.09), TB (10.05±4.85) and CB (3.00±1.67). These mean values were subjected to a statistical test using students t-test which revealed a significant increase (p<0.05).The results suggest that malaria, typhoid and malaria-typhoid co-infection can elevate ALP, AST, ALT, TB and CB serum levels and can lead to liver damage if not properly treated.

  18. Systematic analysis of FKBP inducible degradation domain tagging strategies for the human malaria parasite Plasmodium falciparum.

    Mauro Ferreira de Azevedo

    Full Text Available Targeted regulation of protein levels is an important tool to gain insights into the role of proteins essential to cell function and development. In recent years, a method based on mutated forms of the human FKBP12 has been established and used to great effect in various cell types to explore protein function. The mutated FKBP protein, referred to as destabilization domain (DD tag when fused with a native protein at the N- or C-terminus targets the protein for proteosomal degradation. Regulated expression is achieved via addition of a compound, Shld-1, that stabilizes the protein and prevents degradation. A limited number of studies have used this system to provide powerful insight into protein function in the human malaria parasite Plasmodium falciparum. In order to better understand the DD inducible system in P. falciparum, we studied the effect of Shld-1 on parasite growth, demonstrating that although development is not impaired, it is delayed, requiring the appropriate controls for phenotype interpretation. We explored the quantified regulation of reporter Green Fluorescent Protein (GFP and luciferase constructs fused to three DD variants in parasite cells either via transient or stable transfection. The regulation obtained with the original FKBP derived DD domain was compared to two triple mutants DD24 and DD29, which had been described to provide better regulation for C-terminal tagging in other cell types. When cloned to the C-terminal of reporter proteins, DD24 provided the strongest regulation allowing reporter activity to be reduced to lower levels than DD and to restore the activity of stabilised proteins to higher levels than DD29. Importantly, DD24 has not previously been applied to regulate proteins in P. falciparum. The possibility of regulating an exported protein was addressed by targeting the Ring-Infected Erythrocyte Surface Antigen (RESA at its C-terminus. The tagged protein demonstrated an important modulation of its

  19. The severity of malarial anaemia in Plasmodium chabaudi infections of BALB/c mice is determined independently of the number of circulating parasites

    Lamb Tracey J

    2008-04-01

    Full Text Available Abstract Background Severe malarial anaemia is a major complication of malaria infection and is multi-factorial resulting from loss of circulating red blood cells (RBCs from parasite replication, as well as immune-mediated mechanisms. An understanding of the causes of severe malarial anaemia is necessary to develop and implement new therapeutic strategies to tackle this syndrome of malaria infection. Methods Using analysis of variance, this work investigated whether parasite-destruction of RBCs always accounts for the severity of malarial anaemia during infections of the rodent malaria model Plasmodium chabaudi in mice of a BALB/c background. Differences in anaemia between two different clones of P. chabaudi were also examined. Results Circulating parasite numbers were not correlated with the severity of anaemia in either BALB/c mice or under more severe conditions of anaemia in BALB/c RAG2 deficient mice (lacking T and B cells. Mice infected with P. chabaudi clone CB suffered more severe anaemia than mice infected with clone AS, but this was not correlated with the number of parasites in the circulation. Instead, the peak percentage of parasitized RBCs was higher in CB-infected animals than in AS-infected animals, and was correlated with the severity of anaemia, suggesting that the availability of uninfected RBCs was impaired in CB-infected animals. Conclusion This work shows that parasite numbers are a more relevant measure of parasite levels in P. chabaudi infection than % parasitaemia, a measure that does not take anaemia into account. The lack of correlation between parasite numbers and the drop in circulating RBCs in this experimental model of malaria support a role for the host response in the impairment or destruction of uninfected RBC in P. chabaudi infections, and thus development of acute anaemia in this malaria model.

  20. Malaria infection and disease in an area with pyrethroid-resistant vectors in southern Benin

    Akogbéto Martin

    2010-12-01

    Full Text Available Abstract Background This study aimed to investigate baseline data on malaria before the evaluation of new vector control strategies in an area of pyrethroid-resistance of vectors. The burden of malaria was estimated in terms of infection (prevalence and parasite density and of clinical episodes. Methods Between December 2007 and December 2008 in the health district of Ouidah - Kpomassè - Tori Bossito (southern Benin, a descriptive epidemiological survey of malaria was conducted. From 28 selected villages, seven were randomized from which a total of 440 children aged 0 to 5 years were randomly selected. Clinical and parasitological information was obtained by active case detection of malaria episodes carried out during eight periods of six consecutive days scheduled at six weekly intervals and by cross-sectional surveys of asymptomatic infection. Entomological information was also collected. The ownership, the use and the correct use of long-lasting insecticide-treated nets (LLINs were checked over weekly-survey by unannounced visits at home in the late evening. Results Mean parasite density in asymptomatic children was 586 P. falciparum asexual forms per μL of blood (95%CI 504-680. Pyrogenic parasite cut-off was estimated 2,000 P. falciparum asexual blood forms per μL. The clinical incidence of malaria was 1.5 episodes per child per year (95%CI 1.2-1.9. Parasitological and clinical variables did not vary with season. Anopheles gambiae s.l. was the principal vector closely followed by Anopheles funestus. Entomological inoculation rate was 5.3 (95%CI 1.1-25.9 infective bites per human per year. Frequency of the L1014F kdr (West allele was around 50%. Annual prevalence rate of Plasmodium falciparum asymptomatic infection was 21.8% (95%CI 19.1-24.4 and increased according to age. Mean rates of ownership and use of LLINs were 92% and 70% respectively. The only correct use of LLINs (63% conferred 26% individual protection against only infection (OR

  1. Disrupting Mosquito Reproduction and Parasite Development for Malaria Control.

    Lauren M Childs

    2016-12-01

    Full Text Available The control of mosquito populations with insecticide treated bed nets and indoor residual sprays remains the cornerstone of malaria reduction and elimination programs. In light of widespread insecticide resistance in mosquitoes, however, alternative strategies for reducing transmission by the mosquito vector are urgently needed, including the identification of safe compounds that affect vectorial capacity via mechanisms that differ from fast-acting insecticides. Here, we show that compounds targeting steroid hormone signaling disrupt multiple biological processes that are key to the ability of mosquitoes to transmit malaria. When an agonist of the steroid hormone 20-hydroxyecdysone (20E is applied to Anopheles gambiae females, which are the dominant malaria mosquito vector in Sub Saharan Africa, it substantially shortens lifespan, prevents insemination and egg production, and significantly blocks Plasmodium falciparum development, three components that are crucial to malaria transmission. Modeling the impact of these effects on Anopheles population dynamics and Plasmodium transmission predicts that disrupting steroid hormone signaling using 20E agonists would affect malaria transmission to a similar extent as insecticides. Manipulating 20E pathways therefore provides a powerful new approach to tackle malaria transmission by the mosquito vector, particularly in areas affected by the spread of insecticide resistance.

  2. Parasitic infections in African pangolin ( Manis temminckii ) from Edo ...

    Amblyomma sp.). Oochoristica sp. (100%) and Amblyomma sp. (75%) were the most prevalent parasites. Both male and female pangolins recorded equal prevalence (100%) of infection, however, mean intensity of parasites was higher in males ...

  3. HIV impairs opsonic phagocytic clearance of pregnancy-associated malaria parasites.

    Jessica Keen

    2007-05-01

    Full Text Available BACKGROUND: Primigravid (PG women are at risk for pregnancy-associated malaria (PAM. Multigravid (MG women acquire protection against PAM; however, HIV infection impairs this protective response. Protection against PAM is associated with the production of IgG specific for variant surface antigens (VSA-PAM expressed by chondroitin sulfate A (CSA-adhering parasitized erythrocytes (PEs. We hypothesized that VSA-PAM-specific IgG confers protection by promoting opsonic phagocytosis of PAM isolates and that HIV infection impairs this response. METHODS AND FINDINGS: We assessed the ability of VSA-PAM-specific IgG to promote opsonic phagocytosis of CSA-adhering PEs and the impact of HIV infection on this process. Opsonic phagocytosis assays were performed using the CSA-adherent parasite line CS2 and human and murine macrophages. CS2 PEs were opsonized with plasma or purified IgG subclasses from HIV-negative or HIV-infected PG and MG Kenyan women or sympatric men. Levels of IgG subclasses specific for VSA-PAM were compared in HIV-negative and HIV-infected women by flow cytometry. Plasma from HIV-negative MG women, but not PG women or men, promoted the opsonic phagocytosis of CSA-binding PEs (p < 0.001. This function depended on VSA-PAM-specific plasma IgG1 and IgG3. HIV-infected MG women had significantly lower plasma opsonizing activity (median phagocytic index 46 [interquartile range (IQR 18-195] versus 251 [IQR 93-397], p = 0.006 and levels of VSA-PAM-specific IgG1 (mean fluorescence intensity [MFI] 13 [IQR 11-20] versus 30 [IQR 23-41], p < 0.001 and IgG3 (MFI 17 [IQR 14-23] versus 28 [IQR 23-37], p < 0.001 than their HIV-negative MG counterparts. CONCLUSIONS: Opsonic phagocytosis may represent a novel correlate of protection against PAM. HIV infection may increase the susceptibility of multigravid women to PAM by impairing this clearance mechanism.

  4. Severe malaria - a case of fatal Plasmodium knowlesi infection with post-mortem findings: a case report

    Adem Patricia

    2010-01-01

    Full Text Available Abstract Background Zoonotic malaria caused by Plasmodium knowlesi is an important, but newly recognized, human pathogen. For the first time, post-mortem findings from a fatal case of knowlesi malaria are reported here. Case presentation A formerly healthy 40 year-old male became symptomatic 10 days after spending time in the jungle of North Borneo. Four days later, he presented to hospital in a state of collapse and died within two hours. He was hyponatraemic and had elevated blood urea, potassium, lactate dehydrogenase and amino transferase values; he was also thrombocytopenic and eosinophilic. Dengue haemorrhagic shock was suspected and a post-mortem examination performed. Investigations for dengue virus were negative. Blood for malaria parasites indicated hyperparasitaemia and single species P. knowlesi infection was confirmed by nested-PCR. Macroscopic pathology of the brain and endocardium showed multiple petechial haemorrhages, the liver and spleen were enlarged and lungs had features consistent with ARDS. Microscopic pathology showed sequestration of pigmented parasitized red blood cells in the vessels of the cerebrum, cerebellum, heart and kidney without evidence of chronic inflammatory reaction in the brain or any other organ examined. Brain sections were negative for intracellular adhesion molecule-1. The spleen and liver had abundant pigment containing macrophages and parasitized red blood cells. The kidney had evidence of acute tubular necrosis and endothelial cells in heart sections were prominent. Conclusions The overall picture in this case was one of systemic malaria infection that fit the WHO classification for severe malaria. Post-mortem findings in this case were unexpectedly similar to those that define fatal falciparum malaria, including cerebral pathology. There were important differences including the absence of coma despite petechial haemorrhages and parasite sequestration in the brain. These results suggest that further

  5. Long- and short-term selective forces on malaria parasite genomes

    Nygaard, Sanne; Braunstein, Alexander; Malsen, Gareth

    2010-01-01

    Plasmodium parasites, the causal agents of malaria, result in more than 1 million deaths annually. Plasmodium are unicellular eukaryotes with small ~23 Mb genomes encoding ~5200 protein-coding genes. The protein-coding genes comprise about half of these genomes. Although evolutionary processes ha...

  6. Protein export marks the early phase of gametocytogenesis of the human malaria parasite Plasmodium falciparum.

    Silvestrini, F.; Lasonder, E.; Olivieri, A.; Camarda, G.; Schaijk, B.C.L. van; Sanchez, M.; Younis Younis, S.; Sauerwein, R.W.; Alano, P.

    2010-01-01

    Despite over a century of study of malaria parasites, parts of the Plasmodium falciparum life cycle remain virtually unknown. One of these is the early gametocyte stage, a round shaped cell morphologically similar to an asexual trophozoite in which major cellular transformations ensure subsequent

  7. Cytometric quantification of singlet oxygen in the human malaria parasite Plasmodium falciparum

    Butzloff, Sabine; Groves, Matthew R; Wrenger, Carsten; Müller, Ingrid B

    The malaria parasite Plasmodium falciparum proliferates within human erythrocytes and is thereby exposed to a variety of reactive oxygen species (ROS) such as hydrogen peroxide, hydroxyl radical, superoxide anion, and highly reactive singlet oxygen ((1)O(2)). While most ROS are already well studied

  8. The structural basis for CD36 binding by the malaria parasite

    Hsieh, Fu-Lien; Turner, Louise; Bolla, Jani Reddy

    2016-01-01

    CD36 is a scavenger receptor involved in fatty acid metabolism, innate immunity and angiogenesis. It interacts with lipoprotein particles and facilitates uptake of long chain fatty acids. It is also the most common target of the PfEMP1 proteins of the malaria parasite, Plasmodium falciparum...

  9. Direct and indirect immunosuppression by a malaria parasite in its mosquito vector

    Boëte, C.H.J.J.; Paul, R.E.L.; Koëlla, J.C.

    2004-01-01

    Malaria parasites develop as oocysts within the haemocoel of their mosquito vector during a period that is longer than the average lifespan of many of their vectors. How can they escape from the mosquito's immune responses during their long development? Whereas older oocysts might camouflage

  10. Malaria

    ... less than the risk of catching this infection. Chloroquine has been the drug of choice for protecting against malaria. But because of resistance, it is now only suggested for use in areas where Plasmodium vivax , P. oval , and ...

  11. Subcompartmentalisation of proteins in the rhoptries correlates with ordered events of erythrocyte invasion by the blood stage malaria parasite.

    Elizabeth S Zuccala

    Full Text Available Host cell infection by apicomplexan parasites plays an essential role in lifecycle progression for these obligate intracellular pathogens. For most species, including the etiological agents of malaria and toxoplasmosis, infection requires active host-cell invasion dependent on formation of a tight junction - the organising interface between parasite and host cell during entry. Formation of this structure is not, however, shared across all Apicomplexa or indeed all parasite lifecycle stages. Here, using an in silico integrative genomic search and endogenous gene-tagging strategy, we sought to characterise proteins that function specifically during junction-dependent invasion, a class of proteins we term invasins to distinguish them from adhesins that function in species specific host-cell recognition. High-definition imaging of tagged Plasmodium falciparum invasins localised proteins to multiple cellular compartments of the blood stage merozoite. This includes several that localise to distinct subcompartments within the rhoptries. While originating from the same organelle, however, each has very different dynamics during invasion. Apical Sushi Protein and Rhoptry Neck protein 2 release early, following the junction, whilst a novel rhoptry protein PFF0645c releases only after invasion is complete. This supports the idea that organisation of proteins within a secretory organelle determines the order and destination of protein secretion and provides a localisation-based classification strategy for predicting invasin function during apicomplexan parasite invasion.

  12. Investigating the evolution of apoptosis in malaria parasites: the importance of ecology

    Pollitt Laura C

    2010-11-01

    Full Text Available Abstract Apoptosis is a precisely regulated process of cell death which occurs widely in multicellular organisms and is essential for normal development and immune defences. In recent years, interest has grown in the occurrence of apoptosis in unicellular organisms. In particular, as apoptosis has been reported in a wide range of species, including protozoan malaria parasites and trypanosomes, it may provide a novel target for intervention. However, it is important to understand when and why parasites employ an apoptosis strategy before the likely long- and short-term success of such an intervention can be evaluated. The occurrence of apoptosis in unicellular parasites provides a challenge for evolutionary theory to explain as organisms are expected to have evolved to maximise their own proliferation, not death. One possible explanation is that protozoan parasites undergo apoptosis in order to gain a group benefit from controlling their density as this prevents premature vector mortality. However, experimental manipulations to examine the ultimate causes behind apoptosis in parasites are lacking. In this review, we focus on malaria parasites to outline how an evolutionary framework can help make predictions about the ecological circumstances under which apoptosis could evolve. We then highlight the ecological considerations that should be taken into account when designing evolutionary experiments involving markers of cell death, and we call for collaboration between researchers in different fields to identify and develop appropriate markers in reference to parasite ecology and to resolve debates on terminology.

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

    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.

  14. A new morphologically distinct avian malaria parasite that fails detection by established polymerase chain reaction-based protocols for amplification of the cytochrome B gene.

    Zehtindjiev, Pavel; Križanauskienė, Asta; Bensch, Staffan; Palinauskas, Vaidas; Asghar, Muhammad; Dimitrov, Dimitar; Scebba, Sergio; Valkiūnas, Gediminas

    2012-06-01

    Plasmodium polymorphum n. sp. (Haemosporida, Plasmodiidae) was found in the skylark, Alauda arvensis (Passeriformes: Alaudidae), during autumnal migration in southern Italy. This organism is illustrated and described based on the morphology of its blood stages. The most distinctive feature of this malaria parasite is the clear preference of its blood stages (trophozoites, meronts, and gametocytes) for immature red blood cells, including erythroblasts. Based on preference of erythrocytic meronts for immature red blood cells, P. polymorphum is most similar to species of the subgenus Huffia . This parasite can be readily distinguished from all other bird malaria parasites, including Plasmodium ( Huffia ) spp., due to preferential development and maturation of its gametocytes in immature red blood cells, a unique character for avian Plasmodium spp. In addition, the margins of nuclei in blood stages of P. polymorphum are markedly smooth and distinct; this is also a distinct diagnostic feature of this parasite. Plasmodium polymorphum has been recorded only in the skylark; it is probably a rare parasite, whose host range and geographical distribution remain unclear. Microscopic examination detected a light infection of Plasmodium relictum (lineage GRW11, parasitemia of 50-fold higher than that of P. relictum and several different primers were tested, we suggest that the failure to amplify P. polymorphum is a more complex problem than why co-infections are commonly overlooked in PCR-based studies. We suggest possible explanations of these results and call for additional research on evolution of mitochondrial genome of hemosporidian parasites.

  15. Parasitic infections of wild rabbits and hares

    Ilić Tamara

    2014-01-01

    Full Text Available The paper presents the most important parasitic infections of wild rabbits and hares, which harmful effect in this animal population is manifested as a gradual weakening of the immune system, reduction in fertility, weight loss and constant exhaustion. Order of Lagomorpha (hares or lagomorphs belongs to superorder of higher mammals which includes the family of rabbits (Leporidae which are represented in Europe as well as the family of whistleblowers (Ochotonidae which live only in North America and Northern regions of Asia. The most important representatives of Leporidae family are European hare (Lepus europeus and wild rabbit (Oryctolagus cuniculus. The most important endoparasitosis of hares and wild rabbits are: coccidiosis, encephalitozoonosis (nosemosis, toxoplasmosis, sarcocystosis, giardiasis, cryptosporidiosis, protostrongylosis, trichostrngylodosis, passalurosis, anoplocephalidosis, cysticercosis and fasciolosis. The most frequent ectoparasites of rabbits and wild hares are fleas, lice and ticks. Reduction in hare population, which is noticed in whole Europe including Serbia, is caused by changed living conditions, quantitatively and qualitatively insufficient nutrition, increased use of herbicides as well as various infectious diseases and the diseases of parasitic etiology. Since wild rabbits and hares pose a threat to health of domestic rabbits and people, knowledge of parasitic fauna of these wild animals is of extreme epizootiological and epidemiological importance.

  16. Transgenic Expression of the Anti-parasitic Factor TEP1 in the Malaria Mosquito Anopheles gambiae.

    Gloria Volohonsky

    2017-01-01

    Full Text Available Mosquitoes genetically engineered to be resistant to Plasmodium parasites represent a promising novel approach in the fight against malaria. The insect immune system itself is a source of anti-parasitic genes potentially exploitable for transgenic designs. The Anopheles gambiae thioester containing protein 1 (TEP1 is a potent anti-parasitic protein. TEP1 is secreted and circulates in the mosquito hemolymph, where its activated cleaved form binds and eliminates malaria parasites. Here we investigated whether TEP1 can be used to create malaria resistant mosquitoes. Using a GFP reporter transgene, we determined that the fat body is the main site of TEP1 expression. We generated transgenic mosquitoes that express TEP1r, a potent refractory allele of TEP1, in the fat body and examined the activity of the transgenic protein in wild-type or TEP1 mutant genetic backgrounds. Transgenic TEP1r rescued loss-of-function mutations, but did not increase parasite resistance in the presence of a wild-type susceptible allele. Consistent with previous reports, TEP1 protein expressed from the transgene in the fat body was taken up by hemocytes upon a challenge with injected bacteria. Furthermore, although maturation of transgenic TEP1 into the cleaved form was impaired in one of the TEP1 mutant lines, it was still sufficient to reduce parasite numbers and induce parasite melanization. We also report here the first use of Transcription Activator Like Effectors (TALEs in Anopheles gambiae to stimulate expression of endogenous TEP1. We found that artificial elevation of TEP1 expression remains moderate in vivo and that enhancement of endogenous TEP1 expression did not result in increased resistance to Plasmodium. Taken together, our results reveal the difficulty of artificially influencing TEP1-mediated Plasmodium resistance, and contribute to further our understanding of the molecular mechanisms underlying mosquito resistance to Plasmodium parasites.

  17. Malaria and helminth co-infection and nutritional status of febrile patients in Southern Ethiopia.

    Degarege, Abraham; Animut, Abebe; Legesse, Mengistu; Medhin, Girmay; Erko, Berhanu

    2014-02-01

    Because the mechanisms by which Plasmodium and helminth parasites affect nutritional status are different, these parasites likely have additive effects when they co-exist in a host. This study aimed to compare the prevalence of undernutrition in patients infected with either Plasmodium or helminths and those co-infected with the two types of parasites. Acute febrile patients suspected of having malaria who attended the outpatient clinic at Dore Bafeno Health Center between December 2010 and February 2011 were examined for Plasmodium parasites using Giemsa-stained thick and thin blood smears and for helminths using the thick Kato-Katz method. Nutritional status was determined using anthropometric indices generated from height and weight measurements. Of the 702 patients examined, 34.5% were infected with helminths alone, 12.3% were infected with Plasmodium alone, and 19.4% co-infected with Plasmodium and intestinal helminths. Out of the patients examined, 44.9% were undernourished. The prevalence of undernutrition was not significantly different between those patients not infected with Plasmodium or helminth species and those infected with Plasmodium or helminth species. The differences in the odds of undernutrition were also not significant between patients who were co-infected with different Plasmodium and helminth species and those with single infections with Plasmodium or helminth species in our multivariable logistic regression model adjusted for the confounding effects of age and sex. The prevalence of undernutrition was comparable in patients infected with Plasmodium or helminths alone and those co-infected with Plasmodium and helminths in Dore Bafeno Health Center, Southern Ethiopia. However, further studies are needed in areas of intense transmission where both parasites are endemic to elucidate whether the impact of Plasmodium and helminth co-infection on undernutrition is additive or multiplicative. Copyright © 2013 King Saud Bin Abdulaziz University for

  18. Parasite-based malaria diagnosis: are health systems in Uganda equipped enough to implement the policy?

    Kyabayinze, Daniel J; Achan, Jane; Nakanjako, Damalie; Mpeka, Betty; Mawejje, Henry; Mugizi, Rukaaka; Kalyango, Joan N; D'Alessandro, Umberto; Talisuna, Ambrose; Jean-Pierre, Van geertruyden

    2012-08-24

    Malaria case management is a key strategy for malaria control. Effective coverage of parasite-based malaria diagnosis (PMD) remains limited in malaria endemic countries. This study assessed the health system's capacity to absorb PMD at primary health care facilities in Uganda. In a cross sectional survey, using multi-stage cluster sampling, lower level health facilities (LLHF) in 11 districts in Uganda were assessed for 1) tools, 2) skills, 3) staff and infrastructure, and 4) structures, systems and roles necessary for the implementing of PMD. Tools for PMD (microscopy and/or RDTs) were available at 30 (24%) of the 125 LLHF. All LLHF had patient registers and 15% had functional in-patient facilities. Three months' long stock-out periods were reported for oral and parenteral quinine at 39% and 47% of LLHF respectively. Out of 131 health workers interviewed, 86 (66%) were nursing assistants; 56 (43%) had received on-job training on malaria case management and 47 (36%) had adequate knowledge in malaria case management. Overall, only 18% (131/730) Ministry of Health approved staff positions were filled by qualified personnel and 12% were recruited or transferred within six months preceding the survey. Of 186 patients that received referrals from LLHF, 130(70%) had received pre-referral anti-malarial drugs, none received pre-referral rectal artesunate and 35% had been referred due to poor response to antimalarial drugs. Primary health care facilities had inadequate human and infrastructural capacity to effectively implement universal parasite-based malaria diagnosis. The priority capacity building needs identified were: 1) recruitment and retention of qualified staff, 2) comprehensive training of health workers in fever management, 3) malaria diagnosis quality control systems and 4) strengthening of supply chain, stock management and referral systems.

  19. Climate change and parasite transmission: how temperature affects parasite infectivity via predation on infective stages

    Goedknegt, M.A.; Welsh, J.E.; Drent, J.; Thieltges, D.

    2015-01-01

    Climate change is expected to affect disease risk in many parasite-host systems, e.g., via an effect of temperature on infectivity (temperature effects). However, recent studies indicate that ambient communities can lower disease risk for hosts, for instance via predation on free-living stages of

  20. Increased prevalence of malaria in HIV-infected pregnant women and its implications for malaria control

    Verhoeff, F. H.; Brabin, B. J.; Hart, C. A.; Chimsuku, L.; Kazembe, P.; Broadhead, R. L.

    1999-01-01

    To examine in pregnant women the relationship between HIV infection and malaria prevalence and to determine, in relation to HIV infection, the effectiveness of sulphadoxine-pyrimethamine in clearing P. falciparum infection. Descriptive cross-sectional analysis of P. falciparum prevalence in pregnant

  1. Natural antibody responses to Plasmodium falciparum MSP3 and GLURP(R0) antigens are associated with low parasite densities in malaria patients living in the Central Region of Ghana

    Amoah, L. E.; Nuvor, S. V.; Obboh, E. K.

    2017-01-01

    Background: Plasmodium falciparum genetic diversity and multiplicity of infection (MOI) are parasite features that have been suggested to influence the acquisition of protective immunity against malaria. This study sought to assess the relationship between MOI and parasite density (PD) in malaria...... and adults diagnosed with uncomplicated P. falciparum malaria. Microscopy was used to estimate P. falciparum parasite density and polymerase chain reaction (PCR) amplification of the polymorphic regions of msp1 (PF3D7-0930300) and msp2 (PF3D7-0206800) was used for parasite genotyping and MOI determination....... The geometric mean (GM) for MOI determined by both msp1 and msp2 genotyping was 1.3 for the entire population and was generally higher in children than in adults. Seropositivity was estimated at 67 and 63% for GLURP(R0) and MSP3 antibodies, respectively, and antibody titers were negatively correlated...

  2. Comparative gene expression profiling of P. falciparum malaria parasites exposed to three different histone deacetylase inhibitors.

    Katherine T Andrews

    Full Text Available Histone deacetylase (HDAC inhibitors are being intensively pursued as potential new drugs for a range of diseases, including malaria. HDAC inhibitors are also important tools for the study of epigenetic mechanisms, transcriptional control, and other important cellular processes. In this study the effects of three structurally related antimalarial HDAC inhibitors on P. falciparum malaria parasite gene expression were compared. The three hydroxamate-based compounds, trichostatin A (TSA, suberoylanilide hydroxamic acid (SAHA; Vorinostat® and a 2-aminosuberic acid derivative (2-ASA-9, all caused profound transcriptional effects, with ~2-21% of genes having >2-fold altered expression following 2 h exposure to the compounds. Only two genes, alpha tubulin II and a hydrolase, were up-regulated by all three compounds after 2 h exposure in all biological replicates examined. The transcriptional changes observed after 2 h exposure to HDAC inhibitors were found to be largely transitory, with only 1-5% of genes being regulated after removing the compounds and culturing for a further 2 h. Despite some structural similarity, the three inhibitors caused quite diverse transcriptional effects, possibly reflecting subtle differences in mode of action or cellular distribution. This dataset represents an important contribution to our understanding of how HDAC inhibitors act on malaria parasites and identifies alpha tubulin II as a potential transcriptional marker of HDAC inhibition in malaria parasites that may be able to be exploited for future development of HDAC inhibitors as new antimalarial agents.

  3. Serological responses and immunity to superinfection with avian malaria in experimentally-infected Hawaii Amakihi

    Atkinson, Carter T.; Dusek, Robert J.; Lease, Julie K.

    2001-01-01

    Six of seven Hawaii Amakihi (Hemignathus virens) with chronic malarial infections had no increases in peripheral parasitemia, declines in food consumption, or loss of body weight when rechallenged with the homologous isolate of Plasmodium relictum 61 to 62 days after initial infection. Five uninfected control amakihi exposed at the same time to infective mosquito bites developed acute infections with high parasitemias. Reductions in food consumption and loss of body weight occurred in all control birds and three of these individuals eventually died. When surviving birds were rechallenged >2 yr later with either the same parasite isolate or an isolate of P. relictum collected on the island of Kauai, all individuals were immune to superinfection. Chronically infected birds developed antibodies to a common suite of malarial antigens ranging in size from 22 to 170 kDa that were detectable as early as 8 days post infection on immunoblots of SDS-polyacrylamide gels. Antibodies to this suite of malarial antigens persisted as long as 1,248 days after initial infection and were consistently detectable at times when parasites were not easily found by microscopy on Giemsa-stained blood smears. The immunoblotting method that is described here appears to be an effective technique for identifying birds with chronic, low-intensity malarial infections when circulating parasites are not easily detectable by microscopy. Hawaiian honeycreepers that are capable of recovering from acute infections develop concomitant immunity to superinfection, making them functionally immune in areas where malaria transmission has become endemic.

  4. Genetic variability and population structure of Plasmodium falciparum parasite populations from different malaria ecological regions of Kenya.

    Ingasia, Luicer A; Cheruiyot, Jelagat; Okoth, Sheila Akinyi; Andagalu, Ben; Kamau, Edwin

    2016-04-01

    Transmission intensity, movement of human and vector hosts, biogeographical features, and malaria control measures are some of the important factors that determine Plasmodium falciparum parasite genetic variability and population structure. Kenya has different malaria ecologies which might require different disease intervention methods. Refined parasite population genetic studies are critical for informing malaria control and elimination strategies. This study describes the genetic diversity and population structure of P. falciparum parasites from the different malaria ecological zones in Kenya. Twelve multi-locus microsatellite (MS) loci previously described were genotyped in 225 P. falciparum isolates collected between 2012 and 2013 from five sites; three in lowland endemic regions (Kisumu, Kombewa, and Malindi) and two in highland, epidemic regions (Kisii and Kericho). Parasites from the lowland endemic and highland epidemic regions of western Kenya had high genetic diversity compared to coastal lowland endemic region of Kenya [Malindi]. The Kenyan parasites had a mean genetic differentiation index (FST) of 0.072 (p=0.011). The multi-locus genetic analysis of the 12 MS revealed all the parasites had unique haplotypes. Significant linkage disequilibrium (LD) was observed in all the five parasite populations. Kisumu had the most significant index of association values (0.16; pKenya after introduction of the artemether-lumefantrine is important in refining the spread of drug resistant strains and malaria transmission for more effective control and eventual elimination of malaria in Kenya. Copyright © 2015. Published by Elsevier B.V.

  5. A novel PCR-based system for the detection of four species of human malaria parasites and Plasmodium knowlesi.

    Kanako Komaki-Yasuda

    Full Text Available A microscopy-based diagnosis is the gold standard for the detection and identification of malaria parasites in a patient's blood. However, the detection of cases involving a low number of parasites and the differentiation of species sometimes requires a skilled microscopist. Although PCR-based diagnostic methods are already known to be very powerful tools, the time required to apply such methods is still much longer in comparison to traditional microscopic observation. Thus, improvements to PCR systems are sought to facilitate the more rapid and accurate detection of human malaria parasites Plasmodium falciparum, P. vivax, P. ovale, and P. malariae, as well as P. knowlesi, which is a simian malaria parasite that is currently widely distributed in Southeast Asia. A nested PCR that targets the small subunit ribosomal RNA genes of malaria parasites was performed using a "fast PCR enzyme". In the first PCR, universal primers for all parasite species were used. In the second PCR, inner-specific primers, which targeted sequences from P. falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi, were used. The PCR reaction time was reduced with the use of the "fast PCR enzyme", with only 65 minutes required to perform the first and second PCRs. The specific primers only reacted with the sequences of their targeted parasite species and never cross-reacted with sequences from other species under the defined PCR conditions. The diagnoses of 36 clinical samples that were obtained using this new PCR system were highly consistent with the microscopic diagnoses.

  6. Lysine acetylation in sexual stage malaria parasites is a target for antimalarial small molecules.

    Trenholme, Katharine; Marek, Linda; Duffy, Sandra; Pradel, Gabriele; Fisher, Gillian; Hansen, Finn K; Skinner-Adams, Tina S; Butterworth, Alice; Ngwa, Che Julius; Moecking, Jonas; Goodman, Christopher D; McFadden, Geoffrey I; Sumanadasa, Subathdrage D M; Fairlie, David P; Avery, Vicky M; Kurz, Thomas; Andrews, Katherine T

    2014-07-01

    Therapies to prevent transmission of malaria parasites to the mosquito vector are a vital part of the global malaria elimination agenda. Primaquine is currently the only drug with such activity; however, its use is limited by side effects. The development of transmission-blocking strategies requires an understanding of sexual stage malaria parasite (gametocyte) biology and the identification of new drug leads. Lysine acetylation is an important posttranslational modification involved in regulating eukaryotic gene expression and other essential processes. Interfering with this process with histone deacetylase (HDAC) inhibitors is a validated strategy for cancer and other diseases, including asexual stage malaria parasites. Here we confirm the expression of at least one HDAC protein in Plasmodium falciparum gametocytes and show that histone and nonhistone protein acetylation occurs in this life cycle stage. The activity of the canonical HDAC inhibitors trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA; Vorinostat) and a panel of novel HDAC inhibitors on early/late-stage gametocytes and on gamete formation was examined. Several compounds displayed early/late-stage gametocytocidal activity, with TSA being the most potent (50% inhibitory concentration, 70 to 90 nM). In contrast, no inhibitory activity was observed in P. falciparum gametocyte exflagellation experiments. Gametocytocidal HDAC inhibitors caused hyperacetylation of gametocyte histones, consistent with a mode of action targeting HDAC activity. Our data identify HDAC inhibitors as being among a limited number of compounds that target both asexual and sexual stage malaria parasites, making them a potential new starting point for gametocytocidal drug leads and valuable tools for dissecting gametocyte biology. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  7. Prevalence Soil Transmitted Helminthiasis and malaria co-infection among pregnant women and risk factors in Gilgel Gibe dam Area, Southwest Ethiopia

    2013-01-01

    Background Malaria and Soil Transmitted Helminthiasis (STH) are co-endemic and major public health problems in Ethiopia. The aim of the study was to assess the prevalence of malaria and STHs co-infection and to determine the association risk factors. Methods A cross-sectional community based study was conducted on 388 pregnant women living in three districts around Gilgel Gibe Dam area, southwestern Ethiopia. Socio-demographic and socio-economic data, single stool sample and blood sample were collected from each participant. Results The prevalence of STH and malaria was 159 (41%) and 45 (11.6%), respectively and the prevalence of STHs/malaria co-infection was 30 (7.7%). Hookworm was the most prevalent 114 (29.4%) soil transmitted helminthiasis infection followed by Ascaris lumbricoides (A. lumbricoides) 58 (15%) and Trichuris trichiura (T. trichiura) 13 (3.4%). Habit of eating soil (Adjusted Odds Ratio (AOR) = 4.64, 95% CI: 1.50-14.36, P=0.008), presence of stagnant water near study participants’ house (AOR=2.99, 95% CI: 1.28-6.99, P=0.012) and habit of using human feces as a fertilizer (AOR= 5.34, 95% CI: 1.99-14.28, P<0.001) were found to be significantly associated with malaria and STH co-infection among the pregnant women. Hookworm parasitic load was positively correlated with malaria parasitic load (r = 0.299, P<0.001) while A. lumbricoides parasitic load was negatively correlated with malaria parasitic load (r = −0.095, P<0.001). Conclusion Intestinal parasite and/or malaria co-infection is a health problem among pregnant women living around Gilgel Gibe dam area. Therefore, intervention including improving sanitation, removing stagnant water, and health education to the pregnant women should be given. PMID:23837685

  8. Prevalence soil transmitted helminthiasis and malaria co-infection among pregnant women and risk factors in Gilgel Gibe Dam area, southwest Ethiopia.

    Getachew, Million; Tafess, Ketema; Zeynudin, Ahmed; Yewhalaw, Delenesaw

    2013-07-09

    Malaria and Soil Transmitted Helminthiasis (STH) are co-endemic and major public health problems in Ethiopia. The aim of the study was to assess the prevalence of malaria and STHs co-infection and to determine the association risk factors. A cross-sectional community based study was conducted on 388 pregnant women living in three districts around Gilgel Gibe Dam area, southwestern Ethiopia. Socio-demographic and socio-economic data, single stool sample and blood sample were collected from each participant. The prevalence of STH and malaria was 159 (41%) and 45 (11.6%), respectively and the prevalence of STHs/malaria co-infection was 30 (7.7%). Hookworm was the most prevalent 114 (29.4%) soil transmitted helminthiasis infection followed by Ascaris lumbricoides (A. lumbricoides) 58 (15%) and Trichuris trichiura (T. trichiura) 13 (3.4%). Habit of eating soil (Adjusted Odds Ratio (AOR) = 4.64, 95% CI: 1.50-14.36, P=0.008), presence of stagnant water near study participants' house (AOR=2.99, 95% CI: 1.28-6.99, P=0.012) and habit of using human feces as a fertilizer (AOR= 5.34, 95% CI: 1.99-14.28, P<0.001) were found to be significantly associated with malaria and STH co-infection among the pregnant women. Hookworm parasitic load was positively correlated with malaria parasitic load (r = 0.299, P<0.001) while A. lumbricoides parasitic load was negatively correlated with malaria parasitic load (r = -0.095, P<0.001). Intestinal parasite and/or malaria co-infection is a health problem among pregnant women living around Gilgel Gibe dam area. Therefore, intervention including improving sanitation, removing stagnant water, and health education to the pregnant women should be given.

  9. Gametogenesis in malaria parasites is mediated by the cGMP-dependent protein kinase.

    Louisa McRobert

    2008-06-01

    Full Text Available Malaria parasite transmission requires differentiation of male and female gametocytes into gametes within a mosquito following a blood meal. A mosquito-derived molecule, xanthurenic acid (XA, can trigger gametogenesis, but the signalling events controlling this process in the human malaria parasite Plasmodium falciparum remain unknown. A role for cGMP was revealed by our observation that zaprinast (an inhibitor of phosphodiesterases that hydrolyse cGMP stimulates gametogenesis in the absence of XA. Using cGMP-dependent protein kinase (PKG inhibitors in conjunction with transgenic parasites expressing an inhibitor-insensitive mutant PKG enzyme, we demonstrate that PKG is essential for XA- and zaprinast-induced gametogenesis. Furthermore, we show that intracellular calcium (Ca2+ is required for differentiation and acts downstream of or in parallel with PKG activation. This work defines a key role for PKG in gametogenesis, elucidates the hierarchy of signalling events governing this process in P. falciparum, and demonstrates the feasibility of selective inhibition of a crucial regulator of the malaria parasite life cycle.

  10. Sex steroids, immune system, and parasitic infections: facts and hypotheses.

    Nava-Castro, Karen; Hernández-Bello, Romel; Muñiz-Hernández, Saé; Camacho-Arroyo, Ignacio; Morales-Montor, Jorge

    2012-07-01

    It has been widely reported that the incidence and the severity of natural parasitic infections are different between males and females of several species, including humans. This sexual dimorphism involves a distinct exposure of males and females to various parasite infective stages, differential effects of sex steroids on immune cells, and direct effects of these steroids on parasites, among others. Typically, for a large number of parasitic diseases, the prevalence and intensity is higher in males than females; however, in several parasitic infections, males are more resistant than females. In the present work, we review the effects of sex hormones on immunity to protozoa and helminth parasites, which are the causal agents of several diseases in humans, and discuss the most recent research related to the role of sex steroids in the complex host-parasite relationship. © 2012 New York Academy of Sciences.

  11. Rapid, low dose X-ray diffractive imaging of the malaria parasite Plasmodium falciparum

    Jones, Michael W.M.; Dearnley, Megan K.; Riessen, Grant A. van; Abbey, Brian; Putkunz, Corey T.; Junker, Mark D.; Vine, David J.; McNulty, Ian; Nugent, Keith A.; Peele, Andrew G.; Tilley, Leann

    2014-01-01

    Phase-diverse X-ray coherent diffractive imaging (CDI) provides a route to high sensitivity and spatial resolution with moderate radiation dose. It also provides a robust solution to the well-known phase-problem, making on-line image reconstruction feasible. Here we apply phase-diverse CDI to a cellular sample, obtaining images of an erythrocyte infected by the sexual stage of the malaria parasite, Plasmodium falciparum, with a radiation dose significantly lower than the lowest dose previously reported for cellular imaging using CDI. The high sensitivity and resolution allow key biological features to be identified within intact cells, providing complementary information to optical and electron microscopy. This high throughput method could be used for fast tomographic imaging, or to generate multiple replicates in two-dimensions of hydrated biological systems without freezing or fixing. This work demonstrates that phase-diverse CDI is a valuable complementary imaging method for the biological sciences and ready for immediate application. - Highlights: • Phase-diverse coherent X-ray diffraction microscopy provides high-resolution and high-contrast images of intact biological samples. • Rapid nanoscale resolution imaging is demonstrated at orders of magnitude lower dose than previously possible. • Phase-diverse coherent X-ray diffraction microscopy is a robust technique for rapid, quantitative, and correlative X-ray phase imaging

  12. Rapid, low dose X-ray diffractive imaging of the malaria parasite Plasmodium falciparum

    Jones, Michael W.M., E-mail: michael.jones@latrobe.edu.au [ARC Centre of Excellence for Coherent X-Ray Science, Department of Physics, La Trobe University, Victoria 3086 (Australia); Dearnley, Megan K. [ARC Centre of Excellence for Coherent X-Ray Science, Department of Biochemistry and Molecular Biology, Bio21 Institute, The University of Melbourne, Victoria 3010 (Australia); Riessen, Grant A. van [ARC Centre of Excellence for Coherent X-Ray Science, Department of Physics, La Trobe University, Victoria 3086 (Australia); Abbey, Brian [ARC Centre of Excellence for Coherent X-Ray Science, Department of Physics, La Trobe University, Victoria 3086 (Australia); Melbourne Centre for Nanofabrication, Victoria 3168 (Australia); Putkunz, Corey T. [ARC Centre of Excellence for Coherent X-Ray Science, School of Physics, The University of Melbourne, Victoria 3010 (Australia); Junker, Mark D. [ARC Centre of Excellence for Coherent X-Ray Science, Department of Physics, La Trobe University, Victoria 3086 (Australia); Vine, David J. [Advanced Photon Source, Argonne National Laboratory, Argonne, IL 60439 (United States); McNulty, Ian [Advanced Photon Source, Argonne National Laboratory, Argonne, IL 60439 (United States); Centre for Nanoscale Materials, Argonne National Laboratory, Argonne, Illinois 60439 (United States); Nugent, Keith A. [ARC Centre of Excellence for Coherent X-Ray Science, Department of Physics, La Trobe University, Victoria 3086 (Australia); Peele, Andrew G. [ARC Centre of Excellence for Coherent X-Ray Science, Department of Physics, La Trobe University, Victoria 3086 (Australia); Australian Synchrotron, 800 Blackburn Road, Clayton 3168 (Australia); Tilley, Leann [ARC Centre of Excellence for Coherent X-Ray Science, Department of Biochemistry and Molecular Biology, Bio21 Institute, The University of Melbourne, Victoria 3010 (Australia)

    2014-08-01

    Phase-diverse X-ray coherent diffractive imaging (CDI) provides a route to high sensitivity and spatial resolution with moderate radiation dose. It also provides a robust solution to the well-known phase-problem, making on-line image reconstruction feasible. Here we apply phase-diverse CDI to a cellular sample, obtaining images of an erythrocyte infected by the sexual stage of the malaria parasite, Plasmodium falciparum, with a radiation dose significantly lower than the lowest dose previously reported for cellular imaging using CDI. The high sensitivity and resolution allow key biological features to be identified within intact cells, providing complementary information to optical and electron microscopy. This high throughput method could be used for fast tomographic imaging, or to generate multiple replicates in two-dimensions of hydrated biological systems without freezing or fixing. This work demonstrates that phase-diverse CDI is a valuable complementary imaging method for the biological sciences and ready for immediate application. - Highlights: • Phase-diverse coherent X-ray diffraction microscopy provides high-resolution and high-contrast images of intact biological samples. • Rapid nanoscale resolution imaging is demonstrated at orders of magnitude lower dose than previously possible. • Phase-diverse coherent X-ray diffraction microscopy is a robust technique for rapid, quantitative, and correlative X-ray phase imaging.

  13. Description, molecular characterisation, diagnostics and life cycle of Plasmodium elongatum (lineage pERIRUB01), the virulent avian malaria parasite.

    Palinauskas, Vaidas; Žiegytė, Rita; Iezhova, Tatjana A; Ilgūnas, Mikas; Bernotienė, Rasa; Valkiūnas, Gediminas

    2016-10-01

    Plasmodium elongatum causes severe avian malaria and is distributed worldwide. This parasite is of particular importance due to its ability to develop and cause lethal malaria not only in natural hosts, but also in non-adapted endemic birds such as the brown kiwi and different species of penguins. Information on vectors of this infection is available but is contradictory. PCR-based analysis indicated the possible existence of a cluster of closely related P. elongatum lineages which might differ in their ability to develop in certain mosquitoes and birds. This experimental study provides information about molecular and morphological characterisation of a virulent P. elongatum strain (lineage pERIRUB01) isolated from a naturally infected European robin, Erithacus rubecula. Phylogenetic analysis based on partial cytochrome b gene sequences showed that this parasite lineage is closely related to P. elongatum (lineage pGRW6). Blood stages of both parasite lineages are indistinguishable, indicating that they belong to the same species. Both pathogens develop in experimentally infected canaries, Serinus canaria, causing death of the hosts. In both these lineages, trophozoites and erythrocytic meronts develop in polychromatic erythrocytes and erythroblasts, gametocytes parasitize mature erythrocytes, exoerythrocytic stages develop in cells of the erythrocytic series in bone marrow and are occasionally reported in spleen and liver. Massive infestation of bone marrow cells is the main reason for bird mortality. We report here on syncytium-like remnants of tissue meronts, which slip out of the bone marrow into the peripheral circulation, providing evidence that the syncytia can be a template for PCR amplification. This finding contributes to better understanding positive PCR amplifications in birds when parasitemia is invisible and improved diagnostics of abortive haemosporidian infections. Sporogony of P. elongatum (pERIRUB01) completes the cycle and sporozoites develop in

  14. Proteins involved in invasion of human red blood cells by malaria parasites

    Ewa Jaśkiewicz

    2010-11-01

    Full Text Available Malaria is a disease caused by parasites of Plasmodium species. It is responsible for around 1-2 million deaths annually, mainly children under the age of 5. It occurs mainly in tropical and subtropical areas.Malaria is caused by five Plasmodium species:[i] P. falciparum, P. malariae, P. vivax, P. knowlesi[/i] and [i]P. ovale[/i]. Mosquitoes spread the disease by biting humans. The malaria parasite has two stages of development: the human stage and the mosquito stage. The first stage occurs in the human body and is divided into two phases: the liver phase and the blood phase.The invasion of erythrocytes by [i]Plasmodium[/i] merozoites is a multistep process of specific protein interactions between the parasite and red blood cell. The first step is the reversible merozoite attachment to the erythrocyte followed by its apical reorientation, then formation of an irreversible “tight” junction and finally entry into the red cell in a parasitophorous vacuole.The blood phase is supported by a number of proteins produced by the parasite. The merozoite surface GPI-anchored proteins (MSP-1, 2, 4, 5, 8 and 10 assist in the process of recognition of susceptible erythrocytes, apical membrane antigen (AMA-1 may be directly responsible for apical reorientation of the merozoite and apical proteins which function in tight junction formation. These ligands are members of two families: Duffy binding-like (DBL and reticulocyte binding-like (RBL proteins. In [i]Plasmodium[/i] [i]falciparum[/i] the DBL family includes: EBA-175, EBA-140 (BAEBL, EBA-181 (JESEBL, EBA-165 (PEBL and EBL-1 ligands.To date, no effective antimalarial vaccine has been developed, but there are several studies for this purpose. Therefore, it is crucial to understand the molecular basis of host cells invasion by parasites. Major efforts are focused on developing a multiantigenic and multiepitope vaccine preventing all steps of [i]Plasmodium[/i] invasion.

  15. Evidence-based annotation of the malaria parasite's genome using comparative expression profiling.

    Yingyao Zhou

    2008-02-01

    Full Text Available A fundamental problem in systems biology and whole genome sequence analysis is how to infer functions for the many uncharacterized proteins that are identified, whether they are conserved across organisms of different phyla or are phylum-specific. This problem is especially acute in pathogens, such as malaria parasites, where genetic and biochemical investigations are likely to be more difficult. Here we perform comparative expression analysis on Plasmodium parasite life cycle data derived from P. falciparum blood, sporozoite, zygote and ookinete stages, and P. yoelii mosquito oocyst and salivary gland sporozoites, blood and liver stages and show that type II fatty acid biosynthesis genes are upregulated in liver and insect stages relative to asexual blood stages. We also show that some universally uncharacterized genes with orthologs in Plasmodium species, Saccharomyces cerevisiae and humans show coordinated transcription patterns in large collections of human and yeast expression data and that the function of the uncharacterized genes can sometimes be predicted based on the expression patterns across these diverse organisms. We also use a comprehensive and unbiased literature mining method to predict which uncharacterized parasite-specific genes are likely to have roles in processes such as gliding motility, host-cell interactions, sporozoite stage, or rhoptry function. These analyses, together with protein-protein interaction data, provide probabilistic models that predict the function of 926 uncharacterized malaria genes and also suggest that malaria parasites may provide a simple model system for the study of some human processes. These data also provide a foundation for further studies of transcriptional regulation in malaria parasites.

  16. Asymptomatic only at first sight: malaria infection among schoolchildren in highland Rwanda.

    Sifft, Kevin C; Geus, Dominik; Mukampunga, Caritas; Mugisha, Jean Claude; Habarugira, Felix; Fraundorfer, Kira; Bayingana, Claude; Ndoli, Jules; Umulisa, Irenee; Karema, Corine; von Samson-Himmelstjerna, George; Aebischer, Toni; Martus, Peter; Sendegeya, Augustin; Gahutu, Jean Bosco; Mockenhaupt, Frank P

    2016-11-14

    Plasmodium infection and malaria in school children are increasingly recognized as a relevant public health problem, but data on actual prevalence and health consequences are insufficient. The present study from highland southern Rwanda aimed at estimating infection prevalence among children attending school, at identifying associated factors and at assessing the clinical consequences of these infections. In a survey including 12 schools in the Huye district of Rwanda, 1089 children aged 6-10 years were clinically and anthropometrically examined, malaria parasites were diagnosed by microscopy and PCR, haemoglobin concentrations were measured, and socio-economic and behavioural parameters as well as medical histories were obtained. Upon examination, the vast majority of children was asymptomatic (fever 2.7%). Plasmodium infection was detected in 22.4% (Plasmodium falciparum, 18.8%); 41% of these were submicroscopic. Independent predictors of infection included low altitude, higher age, preceding antimalarial treatment, and absence of electricity or a bicycle in the household. Plasmodium infection was associated with anaemia (mean haemoglobin difference of -1.2 g/dL; 95% CI, -0.8 to -1.5 g/dL), fever, underweight, clinically assessed malnutrition and histories of fever, tiredness, weakness, poor appetite, abdominal pain, and vomiting. With the exception of underweight, these conditions were also increased at submicroscopic infection. Malaria infection is frequent among children attending school in southern highland Rwanda. Although seemingly asymptomatic in the vast majority of cases, infection is associated with a number of non-specific symptoms in the children´s histories, in addition to the impact on anaemia. This argues for improved malaria surveillance and control activities among school children.

  17. Investigations on anopheline mosquitoes close to the nest sites of chimpanzees subject to malaria infection in Ugandan Highlands

    Krief Sabrina

    2012-04-01

    Full Text Available Abstract Background Malaria parasites (Plasmodium sp., including new species, have recently been discovered as low grade mixed infections in three wild chimpanzees (Pan troglodytes schweinfurthii sampled randomly in Kibale National Park, Uganda. This suggested a high prevalence of malaria infection in this community. The clinical course of malaria in chimpanzees and the species of the vectors that transmit their parasites are not known. The fact that these apes display a specific behaviour in which they consume plant parts of low nutritional value but that contain compounds with anti-malarial properties suggests that the apes health might be affected by the parasite. The avoidance of the night-biting anopheline mosquitoes is another potential behavioural adaptation that would lead to a decrease in the number of infectious bites and consequently malaria. Methods Mosquitoes were collected over two years using suction-light traps and yeast-generated CO2 traps at the nesting and the feeding sites of two chimpanzee communities in Kibale National Park. The species of the female Anopheles caught were then determined and the presence of Plasmodium was sought in these insects by PCR amplification. Results The mosquito catches yielded a total of 309 female Anopheles specimens, the only known vectors of malaria parasites of mammalians. These specimens belonged to 10 species, of which Anopheles implexus, Anopheles vinckei and Anopheles demeilloni dominated. Sensitive DNA amplification techniques failed to detect any Plasmodium-positive Anopheles specimens. Humidity and trap height influenced the Anopheles capture success, and there was a negative correlation between nest numbers and mosquito abundance. The anopheline mosquitoes were also less diverse and numerous in sites where chimpanzees were nesting as compared to those where they were feeding. Conclusions These observations suggest that the sites where chimpanzees build their nests every night might be

  18. PERIPHERAL PARASITAEMIA AND ITS ASSOCIATION WITH PLASMA CYTOKINES LEVELS IN MALARIA-INFECTED PREGNANT WOMEN IN ABA, ABIA STATE, NIGERIA.

    Ifeanyichukwu, M O; Okamgba, O C; Amilo, G I; Nwokorie, E A

    2017-01-01

    Cytokines in pregnant female may not be a normal phenomenon as malarial infection is often associated with strong CD4+ cell activation and up-regulation of pro-inflammatory cytokines. We investigated the relationship between peripheral parasitaemia and plasma levels of cytokines among malaria infected pregnant women in Aba, Abia State, Nigeria. A total of 206 non-HIV positive asymptomatic malaria parasitaemic (n=144) and non-parasitaemic (n=62) pregnant women were recruited for this study alongside 80 non-pregnant women who served as positive (n=40) and negative (n=40) controls. Blood samples were aseptically collected from each subject and tested for HIV and malaria parasites using standard methods. Also, plasma levels of cytokines were measured using Th1/Th2 human cytokine ELISA kits (Abcam, UK). Analysis of Variance and Student's t-test were used for Comparison of groups while Pearson's Correlation Coefficient was used for tests of association. The results revealed a mean parasite density of 685.56±484.55 parasites/µl of blood. Malaria infected pregnant subjects showed significantly higher levels of IFN-γ, TNF-α, IL-4, IL-6 and IL-10 when compared with their non-infected counterparts (P< 0.05). The cytokines evaluated were higher in moderate parasitaemia than mild parasitaemia. Positive correlation existed between peripheral parasite density (PPD) and IL-4 (r= 0.24, P=0.004), PPD and IL-6 (r = 0.35, P = 0.001) as well as PPD and IL-10 (r = 0.29, P = 0.001). This study showed that increase in peripheral parasitaemia increased levels of some plasma cytokines (IL-4, IL-6 and IL-10) but not IFN-γ and TNF-α in the malaria infected pregnant women studied.

  19. Fecal Occult Blood Test and Gastrointestinal Parasitic Infection

    Majed H. Wakid

    2010-01-01

    Full Text Available Stool specimens of 1238 workers in western region of Saudi Arabia were examined for infection with intestinal parasites and for fecal occult blood (FOB to investigate the possibility that enteroparasites correlate to occult intestinal bleeding. Direct smears and formal ether techniques were used for detection of diagnostic stages of intestinal parasites. A commercially available guaiac test was used to detect fecal occult blood. 47.01% of the workers were infected with intestinal parasites including eight helminthes species and eight protozoan species. The results provided no significant evidence (P-value=0.143 that intestinal parasitic infection is in association with positive guaiac FOB test.

  20. Relationship between the entomologic inoculation rate and the force of infection for Plasmodium falciparum malaria.

    Smith, Thomas; Maire, Nicolas; Dietz, Klaus; Killeen, Gerry F; Vounatsou, Penelope; Molineaux, Louis; Tanner, Marcel

    2006-08-01

    We propose a stochastic model for the relationship between the entomologic inoculation rate (EIR) for Plasmodium falciparum malaria and the force of infection in endemic areas. The model incorporates effects of increased exposure to mosquito bites as a result of the growth in body surface area with the age of the host, naturally acquired pre-erythrocytic immunity, and the reduction in the proportion of entomologically assessed inoculations leading to infection, as the EIR increases. It is fitted to multiple datasets from field studies of the relationship between malaria infection and the EIR. We propose that this model can account for non-monotonic relationships between the age of the host and the parasite prevalence and incidence of disease. It provides a parsimonious explanation for the faster acquisition of natural immunity in adults than in children exposed to high EIRs. This forms one component of a new stochastic model for the entire transmission cycle of P. falciparum that we have derived to estimate the potential epidemiologic impact of malaria vaccines and other malaria control interventions.

  1. Intravenous artesunate reduces parasite clearance time, duration of intensive care, and hospital treatment in patients with severe malaria in Europe

    Kurth, Florian; Develoux, Michel; Mechain, Matthieu

    2015-01-01

    Intravenous artesunate improves survival in severe malaria, but clinical trial data from nonendemic countries are scarce. The TropNet severe malaria database was analyzed to compare outcomes of artesunate vs quinine treatment. Artesunate reduced parasite clearance time and duration of intensive...

  2. Faktor Risiko Penularan Malaria Di Jawa Barat (Kajian Epidemiologi Tentang Vektor, Parasit Plasmodium, dan Lingkungan Sebagai Faktor Risiko Kesakitan Malaria

    Lukman Hakim

    2013-02-01

    Full Text Available Abstract. Since the territory is divided with the province of Banten, in West Java there are five regencies that defined as malaria endemie area, there are Ciamis, Tasikmalaya, Garut, Cianjur and Sukabumi. Sufferer, concentrated in southern coastal areas (Indonesian Ocean starting from the beach of Kalipucang at Ciamis up to coast of Cikakak at Sukabumi which borders the province of Banten and also mountain and plantations areas. Malaria morbidity incidence risk factors is differ in each of these endemie areas. In general is the presence of malaria patients without symptoms who can be a source of infection that so difficult to know its existence. Still the number of standing water that can become mosqui­to breeding places of Anopheles spp, such as fish pond, small puddle on the rivers ide, shrimp pond, mangrove forests that potentially at the beginning of the rainy season, the fields during rice that potential when the rice gro wing and the river that potential in the dry season. The existence of high population mobility and also the number of vegetation in the surrounding residential population and the existence of cattle are placed close to settle­ments.Key Words : West Java Province, malaria endemie areas, malaria patients without symp­toms, Anopheles spp.

  3. Parasitic infections of amphibians in the Pendjari Biosphere ...

    Parasitic infections of amphibians in the Pendjari Biosphere Reserve, Benin. ... Results obtained show the possible influence of land-use pattern on parasite distribution. For example, the ... Furthermore, this infection pattern may be indicative of an immunosuppressive effect of pesticides on the frogs of the Agricultural Zone.

  4. Intestinal Parasitic Infections in Primary School Children in Rural ...

    Background: Intestinal parasitic infections are a major public health problem in developing countries where majority of the affected persons are children. This study is aimed at determining the prevalence of intestinal parasitic infections and the effect of socio-demography in some rural primary schools in Ovia Northeast ...

  5. PARASITIC INFECTIONS OF DRY SEASON FARMERS IN SOME ...

    Standard laboratory procedures were adopted in the collection, processing and parasite identification in the stool samples. The rates of parasites infections in the farmers were 91.6% for helminthes and 86.4% for protozoa. Helminth infection rates but not those of protozoa, varied significantly between farmers and controls.

  6. Dual stage synthesis and crucial role of cytoadherence-linked asexual gene 9 in the surface expression of malaria parasite var proteins

    Goel, Suchi; Valiyaveettil, Manojkumar; Achur, Rajeshwara N

    2010-01-01

    adherence. However, how CLAG9 influences this process remains unknown. In this study, we show that CLAG9 interacts with VAR2CSA, a PfEMP1 that mediates IRBC adherence to chondroitin 4-sulfate in the placenta. Importantly, our results show that the adherent parasites synthesize CLAG9 at two stages--the early......Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family members mediate the adherence of parasite-infected red blood cells (IRBCs) to various host receptors. A previous study has shown that the parasite protein, cytoadherence-linked asexual gene 9 (CLAG9), is also essential for IRBC...... within the parasite. Based on these findings, we propose that CLAG9 plays a critical role in the trafficking of PfEMP1s onto the IRBC surface. These results have important implications for the development of therapeutics for cerebral, placental, and other cytoadherence-associated malaria illnesses....

  7. Prospects and Pitfalls of Pregnancy-Associated Malaria Vaccination Based on the Natural Immune Response to Plasmodium falciparum VAR2CSA-Expressing Parasites

    Elizabeth G. Kane

    2011-01-01

    Full Text Available Pregnancy-associated malaria, a manifestation of severe malaria, is the cause of up to 200,000 infant deaths a year, through the effects of placental insufficiency leading to growth restriction and preterm delivery. Development of a vaccine is one strategy for control. Plasmodium falciparum-infected red blood cells accumulate in the placenta through specific binding of pregnancy-associated parasite variants that express the VAR2CSA antigen to chondroitin sulphate A on the surface of syncytiotrophoblast cells. Parasite accumulation, accompanied by an inflammatory infiltrate, disrupts the cytokine balance of pregnancy with the potential to cause placental damage and compromise foetal growth. Multigravid women develop immunity towards VAR2CSA-expressing parasites in a gravidity-dependent manner which prevents unfavourable pregnancy outcomes. Although current vaccine design, targeting VAR2CSA antigens, has succeeded in inducing antibodies artificially, this candidate may not provide protection during the first trimester and may only protect those women living in areas endemic for malaria. It is concluded that while insufficient information about placental-parasite interactions is presently available to produce an effective vaccine, incremental progress is being made towards achieving this goal.

  8. Malaria diagnosis by PCR revealed differential distribution of mono and mixed species infections by Plasmodium falciparum and P. vivax in India.

    Siwal, Nisha; Singh, Upasana Shyamsunder; Dash, Manoswini; Kar, Sonalika; Rani, Swati; Rawal, Charu; Singh, Rajkumar; Anvikar, Anupkumar R; Pande, Veena; Das, Aparup

    2018-01-01

    Malaria is a vector-borne infectious disease, caused by five different species of the genus Plasmodium, and is endemic to many tropical and sub-tropical countries of the globe. At present, malaria diagnosis at the primary health care level in India is conducted by either microscopy or rapid diagnostic test (RDT). In recent years, molecular diagnosis (by PCR assay), has emerged as the most sensitive method for malaria diagnosis. India is highly endemic to malaria and shoulders the burden of two major malaria parasites, Plasmodium falciparum and P. vivax. Previous studies using PCR diagnostic assay had unraveled several interesting facts on distribution of malaria parasites in India. However, these studies had several limitations from small sample size to limited geographical areas of sampling. In order to mitigate these limitations, we have collected finger-prick blood samples from 2,333 malaria symptomatic individuals in nine states from 11 geographic locations, covering almost the entire malaria endemic regions of India and performed all the three diagnostic tests (microscopy, RDT and PCR assay) and also have conducted comparative assessment on the performance of the three diagnostic tests. Since PCR assay turned out to be highly sensitive (827 malaria positive cases) among the three types of tests, we have utilized data from PCR diagnostic assay for analyses and inferences. The results indicate varied distributional prevalence of P. vivax and P. falciparum according to locations in India, and also the mixed species infection due to these two species. The proportion of P. falciparum to P. vivax was found to be 49:51, and percentage of mixed species infections due to these two parasites was found to be 13% of total infections. Considering India is set for malaria elimination by 2030, the present malaria epidemiological information is of high importance.

  9. Experimental evolution, genetic analysis and genome re-sequencing reveal the mutation conferring artemisinin resistance in an isogenic lineage of malaria parasites

    Hunt, Paul

    2010-09-16

    Background: Classical and quantitative linkage analyses of genetic crosses have traditionally been used to map genes of interest, such as those conferring chloroquine or quinine resistance in malaria parasites. Next-generation sequencing technologies now present the possibility of determining genome-wide genetic variation at single base-pair resolution. Here, we combine in vivo experimental evolution, a rapid genetic strategy and whole genome re-sequencing to identify the precise genetic basis of artemisinin resistance in a lineage of the rodent malaria parasite, Plasmodium chabaudi. Such genetic markers will further the investigation of resistance and its control in natural infections of the human malaria, P. falciparum.Results: A lineage of isogenic in vivo drug-selected mutant P. chabaudi parasites was investigated. By measuring the artemisinin responses of these clones, the appearance of an in vivo artemisinin resistance phenotype within the lineage was defined. The underlying genetic locus was mapped to a region of chromosome 2 by Linkage Group Selection in two different genetic crosses. Whole-genome deep coverage short-read re-sequencing (IlluminaSolexa) defined the point mutations, insertions, deletions and copy-number variations arising in the lineage. Eight point mutations arise within the mutant lineage, only one of which appears on chromosome 2. This missense mutation arises contemporaneously with artemisinin resistance and maps to a gene encoding a de-ubiquitinating enzyme.Conclusions: This integrated approach facilitates the rapid identification of mutations conferring selectable phenotypes, without prior knowledge of biological and molecular mechanisms. For malaria, this model can identify candidate genes before resistant parasites are commonly observed in natural human malaria populations. 2010 Hunt et al; licensee BioMed Central Ltd.

  10. PCR diagnostics underestimate the prevalence of avian malaria (Plasmodium relictum) in experimentally-infected passerines

    Jarvi, Susan I.; Schultz, Jeffrey J.; Atkinson, Carter T.

    2002-01-01

    Several polymerase chain reaction (PCR)-based methods have recently been developed for diagnosing malarial infections in both birds and reptiles, but a critical evaluation of their sensitivity in experimentally-infected hosts has not been done. This study compares the sensitivity of several PCR-based methods for diagnosing avian malaria (Plasmodium relictum) in captive Hawaiian honeycreepers using microscopy and a recently developed immunoblotting technique. Sequential blood samples were collected over periods of up to 4.4 yr after experimental infection and rechallenge to determine both the duration and detectability of chronic infections. Two new nested PCR approaches for detecting circulating parasites based on P. relictum 18S rRNA genes and the thrombospondin-related anonymous protein (TRAP) gene are described. The blood smear and the PCR tests were less sensitive than serological methods for detecting chronic malarial infections. Individually, none of the diagnostic methods was 100% accurate in detecting subpatent infections, although serological methods were significantly more sensitive (97%) than either nested PCR (61–84%) or microscopy (27%). Circulating parasites in chronically infected birds either disappear completely from circulation or to drop to intensities below detectability by nested PCR. Thus, the use of PCR as a sole means of detection of circulating parasites may significantly underestimate true prevalence.

  11. Thrombocytopenia in malaria: can platelet counts differentiate malaria from other infections

    Arshad, A.R.

    2015-01-01

    To determine the accuracy of thrombocytopenia as a diagnostic marker for malaria. Study Design: Cross-sectional study. Place and Duration of Study: Department of Medicine, 1 Mountain Medical Battalion (Bagh, Azad Kashmir) from July to September 2013. Methodology: Adult patients presenting with a short history of fever without any localizing symptoms or signs were included. Exclusion criteria included patients with fever of > 7 days duration, those in whom an underlying diagnosis could be easily confirmed on the basis of history and physical examination, those on antibiotics/ antimalarials or antiplatelet agents and patients with Dengue fever. Platelet counts in venous whole blood samples were analysed with Sysmex KX-21 Haematology analyzer. Thick and thin peripheral blood smears were then prepared and examined for malarial parasites. Diagnosis of malaria was established on the basis of smear findings. Results: There were 245 patients in total. Out of the 109 patients with thrombocytopenia, 61 had vivax malaria. Platelets count was normal in 136 patients, including 4 with vivax malaria. Falciparum malaria was not seen in any patient. All cases with malaria were uncomplicated. Various measures of accuracy thus calculated were sensitivity 93.85%, specificity 73.33%, positive predictive value 55.96%, negative predictive value 97.06%, positive likelihood ratio of 3.52, negative likelihood ratio of 0.08, diagnostic odds ratio 41.94 and diagnostic accuracy of 78.78%. Conclusion: Thrombocytopenia has an excellent sensitivity and a very good specificity for vivax malaria. Normal platelet counts provide very strong evidence against malaria as the etiology of fever without a focus. (author)

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

    Otto, Thomas D

    2014-10-30

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

  13. GAMBARAN PENGGUNAAN RAPID DIAGNOSTIC TEST PARASIT MALARIA DI DESA PASIRMUKTI KECAMATAN CINEAM KABUPATEN TASIKMALAYA

    Hubullah Fuadzy

    2013-12-01

    Full Text Available Abstract. High mobility amongst mining workers, demanding officer of Cineam Public Health Center can perform rapid diagnosis to the workers. Nowadays, many techniques are developed to detect the early transmission of malaria, begins from the clinical to the molecular, one of that techniques are Rapid Diagnostic Tests (RDTs. This research has been conducted in the village of Pasirmukti district Cineam, Tasikmalaya in 2012. Objective of this paper is description RDT utilities as rapid diagnosing efforts on families who have family members as mine worker malaria endemic areas. Inclusion criteria for this study were family who have and do not have family members were working as workers in malaria-endemic areas at 2011 or 2012. Respondents were willing to participate in this study would be taken for examination RDT. Respondents were willing to participate in this study amounted to 256 people, and 5 of them positive Plasmodium malaria based on RDTs screening. Respondents who positive for malaria on RDTs test were 4 women with lower education background and work as a housewife, then a men with a background of secondary school education and are currently still as student. RDT is one of the malaria parasite tools which suitable for use in the Pasirmukti Village district Cineam - Tasikmalaya. However, keep in mind on how to storage and use in order to avoid errors both false-positive and false negatives test results.   Keywords: rapid diagnostic tests, malaria, Tasikmalaya Abstrak. Mobilitas yang tinggi penduduk Cineam  menuju wilayah pertambangan emas diluar pulau Jawa, menuntut tenaga kesehatan di Puskesmas Cineam dapat melakukan diagnosa dini penyakit malaria terhadap para pekerja tambang tersebut. Saat ini, banyak dikembangkan teknik untuk mendeteksi penularan penyakit malaria secara dini, mulai dari yang bersifat klinis hingga molekuler, diantaranya adalah Rapid Diagnostic Tests (RDTs. Untuk mengetahui gambaran pemanfaatan RDT di Cineam perlu

  14. Functional characterization of malaria parasites deficient in the K+ channel Kch2

    Ellekvist, Peter; Mlambo, Godfree; Kumar, Nirbhay

    2017-01-01

    parasite P. berghei, the functional significance of K+ channel homologue PbKch2 was studied using targeted gene knock-out. The knockout parasites were characterized in a mouse model in terms of growth-kinetics and infectivity in the mosquito vector. Furthermore, using a tracer-uptake technique with 86Rb...... of forming oocysts in female Anopheles stephensi mosquitoes. 86Rb+ uptake in Kch2-deficient blood-stage P. berghei parasites (Kch2-null) did not differ from that of wild-type (WT) parasites. About two-thirds of the 86Rb+ uptake in WT and in Kch2-null parasites could be inhibited by K+ channel blockers...... and could be inferred to the presence of functional Kch1 in Kch2 knockout parasites. Kch2 is therefore not required for transport of K+ in P. berghei and is not essential to mosquito-stage sporogonic development of the parasite....

  15. Structural basis of malaria parasite lysyl-tRNA synthetase inhibition by cladosporin.

    Khan, Sameena; Sharma, Arvind; Belrhali, Hassan; Yogavel, Manickam; Sharma, Amit

    2014-06-01

    Malaria parasites inevitably develop drug resistance to anti-malarials over time. Hence the immediacy for discovering new chemical scaffolds to include in combination malaria drug therapy. The desirable attributes of new chemotherapeutic agents currently include activity against both liver and blood stage malaria parasites. One such recently discovered compound called cladosporin abrogates parasite growth via inhibition of Plasmodium falciparum lysyl-tRNA synthetase (PfKRS), an enzyme central to protein translation. Here, we present crystal structure of ternary PfKRS-lysine-cladosporin (PfKRS-K-C) complex that reveals cladosporin's remarkable ability to mimic the natural substrate adenosine and thereby colonize PfKRS active site. The isocoumarin fragment of cladosporin sandwiches between critical adenine-recognizing residues while its pyran ring fits snugly in the ribose-recognizing cavity. PfKRS-K-C structure highlights ample space within PfKRS active site for further chemical derivatization of cladosporin. Such derivatives may be useful against additional human pathogens that retain high conservation in cladosporin chelating residues within their lysyl-tRNA synthetase.

  16. Molecular Genetic Analysis of Parasite Survival in P. falciparum Malaria.

    1991-03-15

    conducting research utilizing recombinant DNA technology , the investigator(s) adhered to current guidelines promulgated by the National Institute of Health...oligonucleotides unrelated to the conserved elements of Plasmodium falciparum were used (lane marked random oligo). Furthermore, extracts prepared...once with Ix Trager’s buffer. The following steps were carried out on ice. Erythrocytes were lysed in 0.05% saponin (19). The released parasites were

  17. Membrane-Wrapping Contributions to Malaria Parasite Invasion of the Human Erythrocyte

    Dasgupta, Sabyasachi; Auth, Thorsten; Gov, Nir S.; Satchwell, Timothy J.; Hanssen, Eric; Zuccala, Elizabeth S.; Riglar, David T.; Toye, Ashley M.; Betz, Timo; Baum, Jake; Gompper, Gerhard

    2014-01-01

    The blood stage malaria parasite, the merozoite, has a small window of opportunity during which it must successfully target and invade a human erythrocyte. The process of invasion is nonetheless remarkably rapid. To date, mechanistic models of invasion have focused predominantly on the parasite actomyosin motor contribution to the energetics of entry. Here, we have conducted a numerical analysis using dimensions for an archetypal merozoite to predict the respective contributions of the host-parasite interactions to invasion, in particular the role of membrane wrapping. Our theoretical modeling demonstrates that erythrocyte membrane wrapping alone, as a function of merozoite adhesive and shape properties, is sufficient to entirely account for the first key step of the invasion process, that of merozoite reorientation to its apex and tight adhesive linkage between the two cells. Next, parasite-induced reorganization of the erythrocyte cytoskeleton and release of parasite-derived membrane can also account for a considerable energetic portion of actual invasion itself, through membrane wrapping. Thus, contrary to the prevailing dogma, wrapping by the erythrocyte combined with parasite-derived membrane release can markedly reduce the expected contributions of the merozoite actomyosin motor to invasion. We therefore propose that invasion is a balance between parasite and host cell contributions, evolved toward maximal efficient use of biophysical forces between the two cells. PMID:24988340

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

    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

  19. Factors contributing to delay in parasite clearance in uncomplicated falciparum malaria in children

    Sijuade Abayomi

    2010-02-01

    Full Text Available Abstract Background Drug resistance in Plasmodium falciparum is common in many endemic and other settings but there is no clear recommendation on when to change therapy when there is delay in parasite clearance after initiation of therapy in African children. Methods The factors contributing to delay in parasite clearance, defined as a clearance time > 2 d, in falciparum malaria were characterized in 2,752 prospectively studied children treated with anti-malarial drugs between 1996 and 2008. Results 1,237 of 2,752 children (45% had delay in parasite clearance. Overall 211 children (17% with delay in clearance subsequently failed therapy and they constituted 72% of those who had drug failure, i.e., 211 of 291 children. The following were independent risk factors for delay in parasite clearance at enrolment: age less than or equal to 2 years (Adjusted odds ratio [AOR] = 2.13, 95% confidence interval [CI]1.44-3.15, P 50,000/ul (AOR = 2.21, 95% CI = 1.77-2.75, P 20000/μl a day after treatment began, were independent risk factors for delay in clearance. Non-artemisinin monotherapies were associated with delay in clearance and treatment failures, and in those treated with chloroquine or amodiaquine, with pfmdr 1/pfcrt mutants. Delay in clearance significantly increased gametocyte carriage (P Conclusion Delay in parasite clearance is multifactorial, is related to drug resistance and treatment failure in uncomplicated malaria and has implications for malaria control efforts in sub-Saharan Africa.

  20. Behavioural effects of fungal infection by Metarhizium anisopliae in adult malaria mosquitoes

    Ondiaka, S.N.

    2012-01-01

    Malaria remains a major global health problem with the burden of disease greatest in Sub-Saharan Africa. The strategies for malaria control differ throughout the world according to levels of endemicity and the magnitude of disease but the focus remains either to control malaria parasites or

  1. Recognition of Plasmodium falciparum mature gametocyte-infected erythrocytes by antibodies of semi-immune adults and malaria-exposed children from Gabon

    Gebru, Tamirat; Ajua, Anthony; Theisen, Michael

    2017-01-01

    BACKGROUND: Transmission of malaria from man to mosquito depends on the presence of gametocytes, the sexual stage of Plasmodium parasites in the infected host. Naturally acquired antibodies against gametocytes exist and may play a role in controlling transmission by limiting the gametocyte...... falciparum mature gametocytes were investigated in sera of semi-immune adults and malaria-exposed children. In addition, the effect of immunization with GMZ2, a blood stage malaria vaccine candidate, and the effect of intestinal helminth infection on the development of immunity to gametocytes of P...... was significantly higher after fixation and permeabilization of parasitized erythrocytes. Following vaccination with the malaria vaccine candidate GMZ2, anti-gametocyte Ab concentration decreased in adults compared to baseline. Ab response to whole asexual stage antigens had a significant but weak positive...

  2. Co-infections of malaria and geohelminthiasis in two rural communities of Nkassomo and Vian in the Mfou health district, Cameroon.

    Francis Zeukeng

    2014-10-01

    Full Text Available Human co-infection with malaria and helmimths is ubiquitous throughout Africa. Nevertheless, its public health significance on malaria severity remains poorly understood.To contribute to a better understanding of epidemiology and control of this co-infection in Cameroon, a cross-sectional study was carried out to assess the prevalence of concomitant intestinal geohelminthiasis and malaria, and to evaluate its association with malaria and anaemia in Nkassomo and Vian. Finger prick blood specimens from a total of 263 participants aged 1-95 years were collected for malaria microscopy, assessment of haemoglobin levels, and molecular identification of Plasmodium species by PCR. Fresh stool specimens were also collected for the identification and quantification of geohelminths by the Kato-Katz method. The prevalence of malaria, geohelminths, and co-infections were 77.2%, 28.6%, and 22.1%, respectively. Plasmodium falciparum was the only malaria parasite species identified with mean parasite density of 111 (40; 18,800 parasites/µl of blood. The geohelminths found were Ascaris lumbricoides (21.6% and Trichuris trichiura (10.8%, with mean parasite densities of 243 (24; 3,552 and 36 (24; 96 eggs/gram of faeces, respectively. Co-infections of A. lumbricoides and P. falciparum were the most frequent and correlated positively. While no significant difference was observed on the prevalences of single and co-infections between the two localities, there was a significant difference in the density of A. lumbricoides infection between the two localities. The overall prevalence of anaemia was 42%, with individuals co-infected with T. trichiura and P. falciparum (60% being the most at risk. While the prevalence of malaria and anaemia were inversely related to age, children aged 5-14 years were more susceptible to geohelminthiasis and their co-infections with malaria.Co-existence of geohelminths and malaria parasites in Nkassomo and Vian enhances the occurrence of

  3. Host social behavior and parasitic infection: A multifactorial approach

    Ezenwa, V.O.

    2004-01-01

    I examined associations between several components of host social organization, including group size and gregariousness, group stability, territoriality and social class, and gastrointestinal parasite load in African bovids. At an intraspecific level, group size was positively correlated with parasite prevalence, but only when the parasite was relatively host specific and only among host species living in stable groups. Social class was also an important predictor of infection rates. Among gazelles, territorial males had higher parasite intensities than did either bachelor males or females and juveniles, suggesting that highly territorial individuals may be either more exposed or more susceptible to parasites. Associations among territoriality, grouping, and parasitism were also found across taxa. Territorial host genera were more likely to be infected with strongyle nematodes than were nonterritorial hosts, and gregarious hosts were more infected than were solitary hosts. Analyses also revealed that gregariousness and territoriality had an interactive effect on individual parasite richness, whereby hosts with both traits harbored significantly more parasite groups than did hosts with only one or neither trait. Overall, study results indicate that multiple features of host social behavior influence infection risk and suggest that synergism between traits also has important effects on host parasite load.

  4. Severe Malaria Infections Impair Germinal Center Responses by Inhibiting T Follicular Helper Cell Differentiation

    Victoria Ryg-Cornejo

    2016-01-01

    Full Text Available Naturally acquired immunity to malaria develops only after years of repeated exposure to Plasmodium parasites. Despite the key role antibodies play in protection, the cellular processes underlying the slow acquisition of immunity remain unknown. Using mouse models, we show that severe malaria infection inhibits the establishment of germinal centers (GCs in the spleen. We demonstrate that infection induces high frequencies of T follicular helper (Tfh cell precursors but results in impaired Tfh cell differentiation. Despite high expression of Bcl-6 and IL-21, precursor Tfh cells induced during infection displayed low levels of PD-1 and CXCR5 and co-expressed Th1-associated molecules such as T-bet and CXCR3. Blockade of the inflammatory cytokines TNF and IFN-γ or T-bet deletion restored Tfh cell differentiation and GC responses to infection. Thus, this study demonstrates that the same pro-inflammatory mediators that drive severe malaria pathology have detrimental effects on the induction of protective B cell responses.

  5. Detection of Malaria parasite species based on 18S rRNA and assessment of its resistance to the drug for DHPS gene to support the development of irradiation Malaria vaccine

    Mukh Syaifudin; Darlina; Siti Nurhayati

    2016-01-01

    Malaria remains a major public health problem because it causes 1-2 million mortality per year. Therefore the development of its vaccine, including vaccine created by ionizing radiation, is urgently needed to control the disease. Aim of this research was to determine the species of malaria parasite infecting the blood of malaria suspected patients and its resistance to sulfadoxine-pyrimethamine (SP). The number of samples used were 10 blood specimens that obtained from Dok II Hospital in Jayapura. Microscopic examination on thin blood smear was done according to standard procedure, followed by Polymerase Chain Reaction (PCR) based diagnosis to further confirm the parasite using 18S rRNA gene on deoxyribonucleic acid extract. The presence of mutation in the dhps (dihydropteroate synthetase) gene related to SP drugs was examined using restriction fragment length polymorphism (RFLP) method. Results showed that 9 samples were infected with Plasmodium falciparum and 1 infected with P. vivax. Allelic mutants of dhps gene at codon K540E were detected in 3 (33.3%) samples. Even though only in very limited number of samples analyzed, the information obtained will be a great value in additional knowledge for vaccine development with irradiation. (author)

  6. Culture adaptation of malaria parasites selects for convergent loss-of-function mutants.

    Claessens, Antoine; Affara, Muna; Assefa, Samuel A; Kwiatkowski, Dominic P; Conway, David J

    2017-01-24

    Cultured human pathogens may differ significantly from source populations. To investigate the genetic basis of laboratory adaptation in malaria parasites, clinical Plasmodium falciparum isolates were sampled from patients and cultured in vitro for up to three months. Genome sequence analysis was performed on multiple culture time point samples from six monoclonal isolates, and single nucleotide polymorphism (SNP) variants emerging over time were detected. Out of a total of five positively selected SNPs, four represented nonsense mutations resulting in stop codons, three of these in a single ApiAP2 transcription factor gene, and one in SRPK1. To survey further for nonsense mutants associated with culture, genome sequences of eleven long-term laboratory-adapted parasite strains were examined, revealing four independently acquired nonsense mutations in two other ApiAP2 genes, and five in Epac. No mutants of these genes exist in a large database of parasite sequences from uncultured clinical samples. This implicates putative master regulator genes in which multiple independent stop codon mutations have convergently led to culture adaptation, affecting most laboratory lines of P. falciparum. Understanding the adaptive processes should guide development of experimental models, which could include targeted gene disruption to adapt fastidious malaria parasite species to culture.

  7. Malaria epidemiology in low-endemicity areas of the northern coast of Ecuador: high prevalence of asymptomatic infections.

    Sáenz, Fabián E; Arévalo-Cortés, Andrea; Valenzuela, Gabriela; Vallejo, Andrés F; Castellanos, Angélica; Poveda-Loayza, Andrea C; Gutierrez, Juan B; Alvarez, Alvaro; Yan, Yi Heng; Benavides, Yoldy; Castro, Luis Enrique; Arévalo-Herrera, Myriam; Herrera, Sócrates

    2017-07-26

    The recent scale-up in malaria control measures in Latin America has resulted in a significant decrease in the number of reported cases in several countries including Ecuador, where it presented a low malaria incidence in recent years (558 reported cases in 2015) with occasional outbreaks of both Plasmodium falciparum and Plasmodium vivax in the coastal and Amazonian regions. This success in malaria control in recent years has led Ecuador to transition its malaria policy from control to elimination. This study evaluated the general knowledge, attitude and practices (KAP) about malaria, as well as its prevalence in four communities of an endemic area in northwest Ecuador. A total of 258 interviews to assess KAP in the community indicated that most people in the study area have a basic knowledge about the disease but did not use to contribute to its control. Six hundred and forty-eight blood samples were collected and analysed by thick blood smear and real-time PCR. In addition, the distribution of the infections was mapped in the study communities. Although, no parasites were found by microscopy, by PCR the total malaria prevalence was 7.5% (6.9% P. vivax and 0.6% P. falciparum), much higher than expected and comparable to that reported in endemic areas of neighbouring countries with higher malaria transmission. Serology using ELISA and immunofluorescence indicated 27% respondents for P. vivax and 22% respondents for P. falciparum. Results suggest that despite a great malaria reduction in Ecuador, transition from control to elimination would demand further improvement in malaria diagnostics, including active case detection to identify and treat parasite asymptomatic carriers, as well as community participation in its elimination.

  8. Malaria parasite evasion of classical complement pathway attack

    Larsen, Mads Delbo; Ditlev, Sisse; Olmos, Rafael Bayarri

    2017-01-01

    of the protective antibodies that are gradually acquired in response to P. falciparum-IEs. Although this response is dominated by IgG1 and IgG3, complement-mediated attack following activation of the classical pathway does not appear to be a major effector mechanism. We hypothesized that this is related to the knob...... is that the knob-restricted expression of PfEMP1 on the IE surface may serve as a hitherto unappreciated immune evasion mechanism employed by P. falciparum parasites....

  9. Antibodies to variable Plasmodium falciparum-infected erythrocyte surface antigens are associated with protection from novel malaria infections

    Giha, H A; Staalsoe, T; Dodoo, D

    2000-01-01

    is maintained at low densities. Here, we test the hypothesis that the presence or absence of antibodies against variant antigens on the surface of P. falciparum-infected erythrocytes protect individuals against some infectious challenges and render them susceptible to others. Plasma collected in Daraweesh...... susceptible and protected individuals. Together, the results indicate that pre-existing anti-PfEMP1 antibodies can reduce the risk of contracting clinical malaria when challenged by novel parasite clones expressing homologous, but not heterologous variable surface antigens. The results also confirm...

  10. Malaria infection and life-style factors among hilltribes along the Thai-Myanmar border area, northern Thailand.

    Pichainarong, Natchaporn; Chaveepojnkamjorn, Wisit

    2004-12-01

    A cross sectional study was conducted between January, 2001 and June, 2002 to determine the life-style factors associated with malaria infection among hilltribes in the Chiang Rai Province, Mae Fah Luang district located along the Thai-Myanmar border, northern Thailand. The data collected were a thick blood film examination and a face-to-face interview using a local language interviewer at a mobile clinic or a home visit. The chi-square test, odds ratio, 95% confidence interval and multiple logistic regression were used as data analysis. P. vivax (61.3%) was detected more than P falciparum (38.2%). Parasitic infection was seen in 45.8% of a total of 417 blood examinations. The study area was in a valley covered with forests and small streams, which was ideal for a malaria epidemic. The communities were distributed along different ethnic groups. There were 12 ethnic groups, dominated by the Muser, Eko, and Akha tribes (60-70%). The risk factors included living or working in the forest, accompanying their family during movement through the forest, age < or =14 years (40.9%), poor knowledge of how to protect against malaria (75-80%), and unavailability of protection against malaria via long sleeved clothes, topical repellents, and insecticide treated nets (use and carry), which resulted in an increased exposure to malaria and risk for malaria infection.

  11. Microbial hara-kiri: Exploiting lysosomal cell death in malaria parasites

    Jun-Hong Ch’ng

    2015-01-01

    Full Text Available The antimalarial drug chloroquine (CQ has been sidelined in the fight against falciparum malaria due to wide-spread CQ resistance. Replacement drugs like sulfadoxine, pyrimethamine and mefloquine have also since been surpassed with the evolution of multi-drug resistant parasites. Even the currently recommended artemisinin-based combination therapies show signs of compromise due to the recent spread of artemisinin delayed-clearance parasites. Though there have been promising breakthroughs in the pursuit of new effective antimalarials, the development and strategic deployment of such novel chemical entities takes time. We therefore argue that there is a crucial need to re-examine the usefulness of ‘outdated’ drugs like chloroquine, and explore if they might be effective alternative therapies in the interim. We suggest that a novel parasite cell death (pCD pathway may be exploited through the reformulation of CQ to address this need.

  12. Undigested Pills in Stool Mimicking Parasitic Infection.

    Mir, Fazia; Achakzai, Ilyas; Ibdah, Jamal A; Tahan, Veysel

    2017-01-01

    Background . Orally ingested medications now come in both immediate release and controlled release preparations. Controlled release preparations were developed by pharmaceutical companies to improve compliance and decrease frequency of pill ingestion. Case Report . A 67-year-old obese male patient presented to our clinic with focal abdominal pain that had been present 3 inches below umbilicus for the last three years. This pain was not associated with any trauma or recent heavy lifting. Upon presentation, the patient reported that for the last two months he started to notice pearly oval structures in his stool accompanying his chronic abdominal pain. This had coincided with initiation of his nifedipine pills for his hypertension. He reported seeing these undigested pills daily in his stool. Conclusion . The undigested pills may pose a cause of concern for both patients and physicians alike, as demonstrated in this case report, because they can mimic a parasitic infection. This can result in unnecessary extensive work-up. It is important to review the medication list for extended release formulations and note that the outer shell can be excreted whole in the stool.

  13. Pengembangan Mikroskop Dengan Mikrokontroler dan Cahaya Monokromatik Untuk Mendeteksi Parasit Malaria

    Ida Susanti

    2017-10-01

    Full Text Available Malaria still become one of major health burden in Indonesia especially in remote areas of east Indonesia. Golden standard of malaria parasite detection is still microscopic technique using polychromatic light source whether from halogen or natural light source. A microscopic technique has a lot of benefits but still have weaknesses, such as time-consuming and bias on the reading by microscopist, because of artifact in the image. Aims of this study were to designed malaria parasites detection tool that is robust, fast, convenient and clear by minimizing artifact on the slide. Design of this study was laboratory experimental which modified simple microscope into an automatic microscope with table movement and webcam recording using a microcontroller and monochromatic light source. The wavelength of the light sources was 402nm(blue, 532 nm (green and 650 nm (red, the intensity of each source differed. The reading of the slide image was conducted by two certified microscopists, who read 60 images of a thick and thin slide with three different live stage of Plasmodium falciparum live, which wearing, trophozoite and schizont. This study showed that modification of microscope was succeeded with automatic movement and webcam recording, process time in one step movement and recording approximately 10 seconds or 17minutes for 100 fields of view as confirmation process. The monochromatic light source has proven to give a clear and contrast field of view when the intensities were higher than 40 mW and the certified microscopist able to identified Plasmodium falciparum parasites. Data analysis of microscopist reading used nonparametric statistic Friedman by SPSS showed that correlation between images using monochromatic and polychromatic lights have meaningless differences in a thick and thin slide. However, hemozoin as a marker of Plasmodium falciparum parasite was less detected by monochromatic light used in this study.

  14. Comparative haematological parameters of HbAA and HbAS genotype children infected with Plasmodium falciparum malaria in Yemen.

    Albiti, Anisa H; Nsiah, Kwabena

    2014-04-01

    Sickle haemoglobin (HbS) is known to offer considerable protection against falciparum malaria. However, the mechanism of protection is not yet completely understood. In this study, we investigate how the presence of the sickle cell trait affects the haematological profile of AS persons with malaria, in comparison with similarly infected persons with HbAA. This study is based on the hypothesis that the sickle cell trait plays a protective role against malaria. Children from an endemic malaria transmission area in Yemen were enrolled in this study. Hematological parameters were estimated using manual methods, the percentage of parasite density on stained thin smear was calculated, haemoglobin genotypes were determined on paper electrophoresis, ferritin was measured using enzyme-linked immunosorbent assay, serum iron and TIBC were assayed using spectrophotometer, transferrin saturation index was calculated by dividing serum iron by TIBC and expressing the result as a percentage. Haematological parameters were compared in HbAA- and HbAS-infected children. Falciparum malaria parasitaemia was confirmed in the blood smears of 62 children, 44 (55.7%) of AA and 18 (37.5%) AS, so there was higher prevalence in HbAA children (P = 0.047). Parasite density was lower in HbAS- than HbAA-infected children (P = 0.003). Anaemia was prominent in malaria-infected children, with high proportions of moderate and severe forms in HbAA (P = 0.001). The mean levels of haemoglobin, packed cell volume, reticulocyte count, platelets count, lymphocytes, eosinophils, and serum iron were significantly lower while total leukocytes, immature granulocytes, monocytes, erythrocyte sedimentation rate, transferrin saturation, and serum ferritin were significantly higher in HbAA-infected children than HbAS-infected children. Infection with Plasmodium falciparum malaria caused more significant haematological alterations of HbAA children than HbAS. This study supports the observation that sickle cell trait

  15. Cardiac complication after experimental human malaria infection: a case report

    Druilhe Pierre

    2009-12-01

    Full Text Available Abstract A 20 year-old healthy female volunteer participated in a clinical Phase I and IIa safety and efficacy trial with candidate malaria vaccine PfLSA-3-rec adjuvanted with aluminium hydroxide. Eleven weeks after the third and last immunization she was experimentally infected by bites of Plasmodium falciparum-infected mosquitoes. When the thick blood smear became positive, at day 11, she was treated with artemether/lumefantrine according to protocol. On day 16 post-infection i.e. two days after completion of treatment, she woke up with retrosternal chest pain. She was diagnosed as acute coronary syndrome and treated accordingly. She recovered quickly and her follow-up was uneventful. Whether the event was related to the study procedures such as the preceding vaccinations, malaria infection or antimalarial drugs remains elusive. However, the relation in time with the experimental malaria infection and apparent absence of an underlying condition makes the infection the most probable trigger. This is in striking contrast, however, with the millions of malaria cases each year and the fact that such complication has never been reported in the literature. The rare occurrence of cardiac events with any of the preceding study procedures may even support a coincidental finding. Apart from acute coronary syndrome, myocarditis can be considered as a final diagnosis, but the true nature and patho-physiological explanation of the event remain unclear.

  16. Plasmodium falciparum malaria challenge by the bite of aseptic Anopheles stephensi mosquitoes: results of a randomized infectivity trial.

    Kirsten E Lyke

    2010-10-01

    Full Text Available Experimental infection of malaria-naïve volunteers by the bite of Plasmodium falciparum-infected mosquitoes is a preferred means to test the protective effect of malaria vaccines and drugs. The standard model relies on the bite of five infected mosquitoes to induce malaria. We examined the efficacy of malaria transmission using mosquitoes raised aseptically in compliance with current Good Manufacturing Practices (cGMPs.Eighteen adults aged 18-40 years were randomized to receive 1, 3 or 5 bites of Anopheles stephensi mosquitoes infected with the chloroquine-sensitive NF54 strain of P. falciparum. Seventeen participants developed malaria; fourteen occurring on Day 11. The mean prepatent period was 10.9 days (9-12 days. The geometric mean parasitemia was 15.7 parasites/µL (range: 4-70 by microscopy. Polymerase chain reaction (PCR detected parasites 3.1 (range: 0-4 days prior to microscopy. The geometric mean sporozoite load was 16,753 sporozoites per infected mosquito (range: 1,000-57,500. A 1-bite participant withdrew from the study on Day 13 post-challenge and was PCR and smear negative.The use of aseptic, cGMP-compliant P. falciparum-infected mosquitoes is safe, is associated with a precise prepatent period compared to the standard model and appears more efficient than the standard approach, as it led to infection in 100% (6/6 of volunteers exposed to three mosquito bites and 83% (5/6 of volunteers exposed to one mosquito bite.ClinicalTrials.gov NCT00744133.

  17. Mannose-binding lectin is a disease modifier in clinical malaria and may function as opsonin for Plasmodium falciparum-infected erythrocytes

    Garred, Peter; Nielsen, Morten A; Kurtzhals, Jørgen

    2003-01-01

    Variant alleles in the mannose-binding lectin (MBL) gene (mbl2) causing low levels of functional MBL are associated with susceptibility to different infections and are common in areas where malaria is endemic. Therefore, we investigated whether MBL variant alleles in 551 children from Ghana were...... associated with the occurrence and outcome parameters of Plasmodium falciparum malaria and asked whether MBL may function as an opsonin for P. falciparum. No difference in MBL genotype frequency was observed between infected and noninfected children or between children with cerebral malaria and/or severe...... malarial anemia and children with uncomplicated malaria. However, patients with complicated malaria who were homozygous for MBL variant alleles had significantly higher parasite counts and lower blood glucose levels than their MBL-competent counterparts. Distinct calcium-dependent binding of MBL...

  18. Breastfeeding and risk of parasitic infection-a review

    Prameela Kannan Kutty

    2014-11-01

    Full Text Available Breastfeeding, as exclusive nutrition in the first six months of life, is a necessary nutritional requisite in infants. Except for very few maternal diseases that contraindicate breastfeeding, some of which still controversial, breastfeeding mothers must continue exclusive and sustained lactation to provide maximum overall benefits through breastfeeding. Parasitic infections is a global disease and children remain a significant proportion of the affected population. The complex and mandatory life cycles of some parasites, particularly the helminths may partly explain their geographical distribution. The world-wide prevalence of parasitic infections as well as the largely asymptomatic nature of most infections, make many of these infections to likely remain under-recognized. Breast milk, the prime infant nutrition must be recognized to be more than a rare vehicle of parasite transmission, but also a general and focused immune defensive tool against some important parasites. The possibility and influence of small quantities of parasite antigens in breast milk have not been adequately explored. It is believed that useful immunological responses both direct and indirect in breast milk that occur due to the presence of parasite antigens, must be further studied in the light of both immediate and long term benefits. Within this context, and prompted by a spectrum of existing uncertainties, researched and hypothetical roles of parasites and associated immunological responses in the lactating mammary gland are proposed and reviewed.

  19. Parasitic infections associated with febrile conditions in Imo State ...

    Urinary tract parasites, which included Trichomonas. vaginalis and Schistosoma haematobium, were found in 330(6.87%) of the study population and hemoparasites (P. falciparum and Onchocerca spp.) in 1260(26.25%). Mixed infections of gastrointestinal and hemoparasites, gastrointestinal and urinary tract parasites, ...

  20. Impacts of parasite infection on columnaris disease of tilapia

    There is no information available on whether parasite infection will increase the susceptibility of tilapia to Flavobacterium columnare and whether parasite treatment could improve fish survival after F. columnare exposure. Two trials were conducted to evaluate 1) the susceptibility of hybrid tilapi...

  1. The controversy of parasitic infection in pediatric appendicitis: a ...

    ... of the operative findings during surgery. Postoperative complications, if any, and the histopathology reports of the removed appendices were also studied. Patients were divided into two groups according to the presence or the absence of parasites in the appendix lumen. In group I (n= 98), parasitic infection was observed, ...

  2. Protein kinase a dependent phosphorylation of apical membrane antigen 1 plays an important role in erythrocyte invasion by the malaria parasite.

    Kerstin Leykauf

    2010-06-01

    Full Text Available Apicomplexan parasites are obligate intracellular parasites that infect a variety of hosts, causing significant diseases in livestock and humans. The invasive forms of the parasites invade their host cells by gliding motility, an active process driven by parasite adhesion proteins and molecular motors. A crucial point during host cell invasion is the formation of a ring-shaped area of intimate contact between the parasite and the host known as a tight junction. As the invasive zoite propels itself into the host-cell, the junction moves down the length of the parasite. This process must be tightly regulated and signalling is likely to play a role in this event. One crucial protein for tight-junction formation is the apical membrane antigen 1 (AMA1. Here we have investigated the phosphorylation status of this key player in the invasion process in the human malaria parasite Plasmodium falciparum. We show that the cytoplasmic tail of P. falciparum AMA1 is phosphorylated at serine 610. We provide evidence that the enzyme responsible for serine 610 phosphorylation is the cAMP regulated protein kinase A (PfPKA. Importantly, mutation of AMA1 serine 610 to alanine abrogates phosphorylation of AMA1 in vivo and dramatically impedes invasion. In addition to shedding unexpected new light on AMA1 function, this work represents the first time PKA has been implicated in merozoite invasion.

  3. Targeting the master regulator mTOR: a new approach to prevent the neurological of consequences of parasitic infections?

    Sheila Donnelly

    2017-11-01

    Full Text Available Abstract A systematic analysis of 240 causes of death in 2013 revealed that parasitic diseases were responsible for more than one million deaths. The vast majority of these fatalities resulted from protozoan infections presenting with neurological sequelae. In the absence of a vaccine, development of effective therapies is essential to improving global public health. In 2015, an intriguing strategy to prevent cerebral malaria was proposed by Gordon et al. 2015 mBio, 6:e00625. Their study suggested that inhibition of the mammalian target of rapamycin prevented experimental cerebral malaria by blocking the damage to the blood brain barrier and stopping the accumulation of parasitized red blood cells and T cells in the brain. Here, we hypothesize that the same therapeutic strategy could be adopted for other protozoan infections with a brain tropism, to prevent cerebral parasitosis by limiting pathogen replication and preventing immune mediated destruction of brain tissue.

  4. The human malaria parasite Pfs47 gene mediates evasion of the mosquito immune system

    Molina-Cruz, A.; Garver, L.S.; Alabaster, A.; Bangiolo, L.; Haile, A.; Winikor, J.; Ortega, C.; Schaijk, B.C.L. van; Sauerwein, R.W.; Taylor-Salmon, E.; Barillas-Mury, C.

    2013-01-01

    Plasmodium falciparum transmission by Anopheles gambiae mosquitoes is remarkably efficient, resulting in a very high prevalence of human malaria infection in sub-Saharan Africa. A combination of genetic mapping, linkage group selection, and functional genomics was used to identify Pfs47 as a P.

  5. The Performance of a Rapid Diagnostic Test in Detecting Malaria Infection in Pregnant Women and the Impact of Missed Infections

    Williams, John E; Cairns, Matthew; Njie, Fanta

    2016-01-01

    BACKGROUND: Intermittent screening and treatment in pregnancy (ISTp) is a potential strategy for the control of malaria during pregnancy. However, the frequency and consequences of malaria infections missed by a rapid diagnostic test (RDT) for malaria are a concern.METHODS: Primigravidae and secu......BACKGROUND: Intermittent screening and treatment in pregnancy (ISTp) is a potential strategy for the control of malaria during pregnancy. However, the frequency and consequences of malaria infections missed by a rapid diagnostic test (RDT) for malaria are a concern.METHODS: Primigravidae...... in 540 women; these were not associated with maternal anemia, placental malaria, or low birth weight. CONCLUSIONS: The sensitivity of an RDT to detect malaria in primigravidae and secundigravidae was high at enrollment in 3 of 4 countries and, in Ghana, at subsequent ANC visits. In Ghana, RDT negative...... malaria infections were not associated with adverse birth outcomes but missed infections were uncommon....

  6. Host age modulates parasite infectivity, virulence and reproduction.

    Izhar, Rony; Ben-Ami, Frida

    2015-07-01

    Host age is one of the most striking differences among hosts within most populations, but there is very little data on how age-dependent effects impact ecological and evolutionary dynamics of both the host and the parasite. Here, we examined the influence of host age (juveniles, young and old adults) at parasite exposure on host susceptibility, fecundity and survival as well as parasite transmission, using two clones of the water flea Daphnia magna and two clones of its bacterial parasite Pasteuria ramosa. Younger D. magna were more susceptible to infection than older ones, regardless of host or parasite clone. Also, younger-infected D. magna became castrated faster than older hosts, but host and parasite clone effects contributed to this trait as well. Furthermore, the early-infected D. magna produced considerably more parasite transmission stages than late-infected ones, while host age at exposure did not affect virulence as it is defined in models (host mortality). When virulence is defined more broadly as the negative effects of infection on host fitness, by integrating the parasitic effects on host fecundity and mortality, then host age at exposure seems to slide along a negative relationship between host and parasite fitness. Thus, the virulence-transmission trade-off differs strongly among age classes, which in turn affects predictions of optimal virulence. Age-dependent effects on host susceptibility, virulence and parasite transmission could pose an important challenge for experimental and theoretical studies of infectious disease dynamics and disease ecology. Our results present a call for a more explicit stage-structured theory for disease, which will incorporate age-dependent epidemiological parameters. © 2015 The Authors. Journal of Animal Ecology © 2015 British Ecological Society.

  7. Discovery of HDAC inhibitors with potent activity against multiple malaria parasite life cycle stages.

    Hansen, Finn K; Sumanadasa, Subathdrage D M; Stenzel, Katharina; Duffy, Sandra; Meister, Stephan; Marek, Linda; Schmetter, Rebekka; Kuna, Krystina; Hamacher, Alexandra; Mordmüller, Benjamin; Kassack, Matthias U; Winzeler, Elizabeth A; Avery, Vicky M; Andrews, Katherine T; Kurz, Thomas

    2014-07-23

    In this work we investigated the antiplasmodial activity of a series of HDAC inhibitors containing an alkoxyamide connecting-unit linker region. HDAC inhibitor 1a (LMK235), previously shown to be a novel and specific inhibitor of human HDAC4 and 5, was used as a starting point to rapidly construct a mini-library of HDAC inhibitors using a straightforward solid-phase supported synthesis. Several of these novel HDAC inhibitors were found to have potent in vitro activity against asexual stage Plasmodium falciparum malaria parasites. Representative compounds were shown to hyperacetylate P. falciparum histones and to inhibit deacetylase activity of recombinant PfHDAC1 and P. falciparum nuclear extracts. All compounds were also screened in vitro for activity against Plasmodium berghei exo-erythrocytic stages and selected compounds were further tested against late stage (IV and V) P. falciparum gametocytes. Of note, some compounds showed nanomolar activity against all three life cycle stages tested (asexual, exo-erythrocytic and gametocyte stages) and several compounds displayed significantly increased parasite selectivity compared to the reference HDAC inhibitor suberoylanilide hydroxamic acid (SAHA). These data suggest that it may be possible to develop HDAC inhibitors that target multiple malaria parasite life cycle stages. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  8. Phylogenetic profiles of all membrane transport proteins of the malaria parasite highlight new drug targets

    January Weiner 3rd

    2016-08-01

    Full Text Available In order to combat the on-going malaria epidemic, discovery of new drug targets remains vital. Proteins that are essential to survival and specific to malaria parasites are key candidates. To survive within host cells, the parasites need to acquire nutrients and dispose of waste products across multiple membranes. Additionally, like all eukaryotes, they must redistribute ions and organic molecules between their various internal membrane bound compartments. Membrane transport proteins mediate all of these processes and are considered important mediators of drug resistance as well as drug targets in their own right. Recently, using advanced experimental genetic approaches and streamlined life cycle profiling, we generated a large collection of Plasmodium berghei gene deletion mutants and assigned essential gene functions, highlighting potential targets for prophylactic, therapeutic, and transmission-blocking anti-malarial drugs. Here, we present a comprehensive orthology assignment of all Plasmodium falciparum putative membrane transport proteins and provide a detailed overview of the associated essential gene functions obtained through experimental genetics studies in human and murine model parasites. Furthermore, we discuss the phylogeny of selected potential drug targets identified in our functional screen. We extensively discuss the results in the context of the functional assignments obtained using gene targeting available to date.

  9. A novel PCR-based system for the detection of four species of human malaria parasites and Plasmodium knowlesi

    Komaki-Yasuda, Kanako; Vincent, Jeanne Perpétue; Nakatsu, Masami; Kato, Yasuyuki; Ohmagari, Norio

    2018-01-01

    A microscopy-based diagnosis is the gold standard for the detection and identification of malaria parasites in a patient’s blood. However, the detection of cases involving a low number of parasites and the differentiation of species sometimes requires a skilled microscopist. Although PCR-based diagnostic methods are already known to be very powerful tools, the time required to apply such methods is still much longer in comparison to traditional microscopic observation. Thus, improvements to PCR systems are sought to facilitate the more rapid and accurate detection of human malaria parasites Plasmodium falciparum, P. vivax, P. ovale, and P. malariae, as well as P. knowlesi, which is a simian malaria parasite that is currently widely distributed in Southeast Asia. A nested PCR that targets the small subunit ribosomal RNA genes of malaria parasites was performed using a “fast PCR enzyme”. In the first PCR, universal primers for all parasite species were used. In the second PCR, inner-specific primers, which targeted sequences from P. falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi, were used. The PCR reaction time was reduced with the use of the “fast PCR enzyme”, with only 65 minutes required to perform the first and second PCRs. The specific primers only reacted with the sequences of their targeted parasite species and never cross-reacted with sequences from other species under the defined PCR conditions. The diagnoses of 36 clinical samples that were obtained using this new PCR system were highly consistent with the microscopic diagnoses. PMID:29370297

  10. Assessment of humoral immune responses to blood-stage malaria antigens following ChAd63-MVA immunization, controlled human malaria infection and natural exposure.

    Biswas, Sumi; Choudhary, Prateek; Elias, Sean C; Miura, Kazutoyo; Milne, Kathryn H; de Cassan, Simone C; Collins, Katharine A; Halstead, Fenella D; Bliss, Carly M; Ewer, Katie J; Osier, Faith H; Hodgson, Susanne H; Duncan, Christopher J A; O'Hara, Geraldine A; Long, Carole A; Hill, Adrian V S; Draper, Simon J

    2014-01-01

    The development of protective vaccines against many difficult infectious pathogens will necessitate the induction of effective antibody responses. Here we assess humoral immune responses against two antigens from the blood-stage merozoite of the Plasmodium falciparum human malaria parasite--MSP1 and AMA1. These antigens were delivered to healthy malaria-naïve adult volunteers in Phase Ia clinical trials using recombinant replication-deficient viral vectors--ChAd63 to prime the immune response and MVA to boost. In subsequent Phase IIa clinical trials, immunized volunteers underwent controlled human malaria infection (CHMI) with P. falciparum to assess vaccine efficacy, whereby all but one volunteer developed low-density blood-stage parasitemia. Here we assess serum antibody responses against both the MSP1 and AMA1 antigens following i) ChAd63-MVA immunization, ii) immunization and CHMI, and iii) primary malaria exposure in the context of CHMI in unimmunized control volunteers. Responses were also assessed in a cohort of naturally-immune Kenyan adults to provide comparison with those induced by a lifetime of natural malaria exposure. Serum antibody responses against MSP1 and AMA1 were characterized in terms of i) total IgG responses before and after CHMI, ii) responses to allelic variants of MSP1 and AMA1, iii) functional growth inhibitory activity (GIA), iv) IgG avidity, and v) isotype responses (IgG1-4, IgA and IgM). These data provide the first in-depth assessment of the quality of adenovirus-MVA vaccine-induced antibody responses in humans, along with assessment of how these responses are modulated by subsequent low-density parasite exposure. Notable differences were observed in qualitative aspects of the human antibody responses against these malaria antigens depending on the means of their induction and/or exposure of the host to the malaria parasite. Given the continued clinical development of viral vectored vaccines for malaria and a range of other diseases

  11. Assessment of humoral immune responses to blood-stage malaria antigens following ChAd63-MVA immunization, controlled human malaria infection and natural exposure.

    Sumi Biswas

    Full Text Available The development of protective vaccines against many difficult infectious pathogens will necessitate the induction of effective antibody responses. Here we assess humoral immune responses against two antigens from the blood-stage merozoite of the Plasmodium falciparum human malaria parasite--MSP1 and AMA1. These antigens were delivered to healthy malaria-naïve adult volunteers in Phase Ia clinical trials using recombinant replication-deficient viral vectors--ChAd63 to prime the immune response and MVA to boost. In subsequent Phase IIa clinical trials, immunized volunteers underwent controlled human malaria infection (CHMI with P. falciparum to assess vaccine efficacy, whereby all but one volunteer developed low-density blood-stage parasitemia. Here we assess serum antibody responses against both the MSP1 and AMA1 antigens following i ChAd63-MVA immunization, ii immunization and CHMI, and iii primary malaria exposure in the context of CHMI in unimmunized control volunteers. Responses were also assessed in a cohort of naturally-immune Kenyan adults to provide comparison with those induced by a lifetime of natural malaria exposure. Serum antibody responses against MSP1 and AMA1 were characterized in terms of i total IgG responses before and after CHMI, ii responses to allelic variants of MSP1 and AMA1, iii functional growth inhibitory activity (GIA, iv IgG avidity, and v isotype responses (IgG1-4, IgA and IgM. These data provide the first in-depth assessment of the quality of adenovirus-MVA vaccine-induced antibody responses in humans, along with assessment of how these responses are modulated by subsequent low-density parasite exposure. Notable differences were observed in qualitative aspects of the human antibody responses against these malaria antigens depending on the means of their induction and/or exposure of the host to the malaria parasite. Given the continued clinical development of viral vectored vaccines for malaria and a range of other

  12. Malaria helminth co-infections and their contribution for aneamia in febrile patients attending Azzezo health center, Gondar, Northwest Ethiopia: a cross sectional study.

    Alemu, Abebe; Shiferaw, Yitayal; Ambachew, Aklilu; Hamid, Halima

    2012-10-01

    To assess the prevalence of malaria helminth co-infections and their contribution for aneamia in febrile patients attending Azzezo health center, Gondar, Northwest Ethiopia. A cross section study was conducted among febrile patients attending Azezo health center from February-March 30, 2011. Convenient sampling technique was used to select 384 individuals. Both capillary blood and stool were collected. Giemsa stained thick and thin blood film were prepared for identification of Plasmodium species and stool sample was examined by direct wet mount and formalin-ether concentration technique for detection of intestinal helminthes parasites. Haemoglobin concentration was determined using a portable haemoglobin spectrophotometer, Hemocue Hb 201 analyzer. Out of 384 febrile patients examined for malaria parasites, 44 (11.5%) individuals were positive for malaria parasites, of which Plasmodium vivax accounted for 75.0% (33), Plasmodium falciparum for 20.5% (9) infectious, whereas two person (4.5%) had mixed species infection. Prevalence of malaria was higher in males (28) when compared with prevalence in females (16). More than half (207, 53.9%) of study participants had one or more infection. Prevalence was slightly higher in females (109, 52.7%) than in males (98, 47.3%). About helminths, Ascaris lumbricoides was the predominant isolate (62.1%) followed by hookworms (18.4%). Only 22 participants were co-infected with malaria parasite and helminths and co-infection with Ascaris lumbricoides was predominant (45.0%). The prevalence of anemia was 10.9% and co-infection with Plasmodium and helminth parasites was significantly associated with (Pparasitic infections is very crucial to improve health of the affected communities in economically developing countries. Copyright © 2012 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  13. Vitamin B6-Dependent Enzymes in the Human Malaria Parasite Plasmodium falciparum: A Druggable Target?

    Thales Kronenberger

    2014-01-01

    Full Text Available Malaria is a deadly infectious disease which affects millions of people each year in tropical regions. There is no effective vaccine available and the treatment is based on drugs which are currently facing an emergence of drug resistance and in this sense the search for new drug targets is indispensable. It is well established that vitamin biosynthetic pathways, such as the vitamin B6 de novo synthesis present in Plasmodium, are excellent drug targets. The active form of vitamin B6, pyridoxal 5-phosphate, is, besides its antioxidative properties, a cofactor for a variety of essential enzymes present in the malaria parasite which includes the ornithine decarboxylase (ODC, synthesis of polyamines, the aspartate aminotransferase (AspAT, involved in the protein biosynthesis, and the serine hydroxymethyltransferase (SHMT, a key enzyme within the folate metabolism.

  14. No Evidence of Delayed Parasite Clearance after Oral Artesunate Treatment of Uncomplicated Falciparum Malaria in Mali

    Maiga, Amelia W.; Fofana, Bakary; Sagara, Issaka; Dembele, Demba; Dara, Antoine; Traore, Oumar Bila; Toure, Sekou; Sanogo, Kassim; Dama, Souleymane; Sidibe, Bakary; Kone, Aminatou; Thera, Mahamadou A.; Plowe, Christopher V.; Doumbo, Ogobara K.; Djimde, Abdoulaye A.

    2012-01-01

    Plasmodium falciparum resistance to artemisinins by delayed parasite clearance is present in Southeast Asia. Scant data on parasite clearance after artemisinins are available from Africa, where transmission is high, burden is greatest, and artemisinin use is being scaled up. Children 1–10 years of age with uncomplicated malaria were treated with 7 days of artesunate and followed for 28 days. Blood smears were done every 8 hours until negative by light microscopy. Results were compared with a similar study conducted in the same village in 2002–2004. The polymerase chain reaction-corrected cure rate was 100%, identical to 2002–2004. By 24 hours after treatment initiation, 37.0% of participants had cleared parasitemia, compared with 31.9% in 2002–2004 (P = 0.5). The median parasite clearance time was 32 hours. Only one participant still had parasites at 48 hours and no participant presented parasitemia at 72 hours. Artesunate was highly efficacious, with no evidence of delayed parasite clearance. We provide baseline surveillance data for the emergence or dissemination of P. falciparum resistance in sub-Saharan Africa. PMID:22764287

  15. Prevalence of malaria and anaemia in pregnancy in Ibadan, South ...

    The study investigated the episode of malaria infection and anaemia in pregnancy of 226 women. The overall prevalence of malaria infection among pregnant women was 23.08%, while only 7.1% of non-pregnant women were malaria positive. The mean parasite density was significantly higher in the primigravidae than in ...

  16. Minocycline prevents cerebral malaria, confers neuroprotection and increases survivability of mice during Plasmodium berghei ANKA infection.

    Apoorv, Thittayil Suresh; Babu, Phanithi Prakash

    2017-02-01

    Cerebral malaria (CM) is a neurological complication arising due to Plasmodium falciparum or Plasmodium vivax infection. Minocycline, a semi-synthetic tetracycline, has been earlier reported to have a neuroprotective role in several neurodegenerative diseases. In this study, we investigated the effect of minocycline treatment on the survivability of mice during experimental cerebral malaria (ECM). The currently accepted mouse model, C57BL/6 mice infected with Plasmodium berghei ANKA, was used for the study. Infected mice were treated with an intra-peritoneal dose of minocycline hydrochloride, 45mg/kg daily for ten days that led to parasite clearance in blood, brain, liver and spleen on 7th day post-infection; and the mice survived until experiment ended (90days) without parasite recrudescence. Evans blue extravasation assay showed that blood-brain barrier integrity was maintained by minocycline. The tumor necrosis factor-alpha protein level and caspase activity, which is related to CM pathogenesis, was significantly reduced in the minocycline-treated group. Fluoro-Jade® C and hematoxylin-eosin staining of the brains of minocycline group revealed a decrease in degenerating neurons and absence of hemorrhages respectively. Minocycline treatment led to decrease in gene expressions of inflammatory mediators like interferon-gamma, CXCL10, CCL5, CCL2; receptors CXCR3 and CCR2; and hence decrease in T-cell-mediated cerebral inflammation. We also proved that this reduction in gene expressions is irrespective of the anti-parasitic property of minocycline. The distinct ability of minocycline to modulate gene expressions of CXCL10 and CXCR3 makes it effective than doxycycline, a tetracycline used as chemoprophylaxis. Our study shows that minocycline is highly effective in conferring neuroprotection during ECM. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Malaria Transmission Risk Factor In West Java (Epidemiology Study About Vector, Plasmodium parasite and Environmental Risk Factors For Malaria Cases

    Lukman Hakim

    2010-06-01

    Full Text Available Since the territory is divided with the province of Banten, in West Java there are five regencies that defined as malaria endemic area, there are Ciamis, Tasikmalaya, Garut, Cianjur and Sukabumi. Sufferer, concentrated in southern coastal areas (Indonesian Ocean starting from the beach of Kalipucang at Ciamis up to coast of Cikakak at Sukabumi which borders the province of Banten and also mountain and plantations areas. Malaria morbidity incidence risk factors is differ in each of these endemic areas. In general is the presence of malaria patients without symptoms who can be a source of infection that so difficult to know its existence. Still the number of standing water that can become mosqui-to breeding places of Anopheles spp, such as fish pond, small puddle on the riverside, shrimp pond, mangrove forests that potentially at the beginning of the rainy season, the fields during rice that potential when the rice growing and the river that potential in the dry season. The existence of high population mobility and also the number of vegetation in the surrounding residential population and the existence of cattle are placed close to settle-ments.

  18. Evaluation of Malaria Infection In Relation to Age and Residential ...

    Objective: To investigate malaria infection in relation to age and residential area. Design: A cross sectional study. Setting: Kipsamoite Dispensary of Nandi County in Kenya. Subjects: The demographic details and medical history for all consenting patients was taken by the clinical officer/nurse. Intervention: Clinical ...

  19. Anemia, malaria and hookworm infections in a Vietnamese ethnic minority

    Le Hung, Q.; de Vries, Peter J.; Giao, Phan T.; Binh, Tran Q.; Nam, Nguyen V.; Kager, Piet A.

    2005-01-01

    The aim of this study was to determine the prevalence of anemia and evaluate the relationship of malaria and helminth infections on anemia status in Phan Tien village, a mountainous ethnic minority community in southern Vietnam. This longitudinal study was performed from April 1997 to 2000 by

  20. Molecular cloning of a K+ channel from the malaria parasite Plasmodium falciparum

    Ellekvist, Peter; Ricke, Christina Høier; Litman, Thomas

    2004-01-01

    In most living cells, K(+) channels are important for the generation of the membrane potential and for volume regulation. The parasite Plasmodium falciparum, which causes malignant malaria, must be able to deal with large variations in the ambient K(+) concentration: it is exposed to high...... concentrations of K(+) when inside the erythrocyte and low concentrations when in plasma. In the recently published genome of P. falciparum, we have identified a gene, pfkch1, encoding a potential K(+) channel, which to some extent resembles the big-conductance (BK) K(+) channel. We have cloned the approximately...

  1. Malaria's Missing Number: Calculating the Human Component of R0 by a Within-Host Mechanistic Model of Plasmodium falciparum Infection and Transmission

    Johnston, Geoffrey L.; Smith, David L.; Fidock, David A.

    2013-01-01

    Human infection by malarial parasites of the genus Plasmodium begins with the bite of an infected Anopheles mosquito. Current estimates place malaria mortality at over 650,000 individuals each year, mostly in African children. Efforts to reduce disease burden can benefit from the development of mathematical models of disease transmission. To date, however, comprehensive modeling of the parameters defining human infectivity to mosquitoes has remained elusive. Here, we describe a mechanistic wi...

  2. Maternally transmitted antibodies to pregnancy-associated variant antigens on the surface of erythrocytes infected with Plasmodium falciparum: relation to child susceptibility to malaria

    Cot, Michel; Le Hesran, Jean Yves; Staalsoe, Trine

    2003-01-01

    The consequences of pregnancy-associated malaria on a child's health have been poorly investigated. Malarial infection of the placenta seems to result in a higher susceptibility of children to the parasite during their first year of life. In 1993-1995, the authors investigated the role of antibod......The consequences of pregnancy-associated malaria on a child's health have been poorly investigated. Malarial infection of the placenta seems to result in a higher susceptibility of children to the parasite during their first year of life. In 1993-1995, the authors investigated the role......, Cameroon. These newborns were subsequently followed up for 2 years to determine the date of first occurrence of blood parasites and mean parasite density during follow-up. Maternally transmitted antibodies to VSA expressed by CSA-binding parasites, but not antibodies to any other specificity, were...... negatively related to time of first appearance of Plasmodium falciparum in a child's blood and were positively related to mean parasite density during the first 2 years of life. If maternal infection is thought to be the main mechanism influencing susceptibility of the newborn to malaria, antibodies to VSA...

  3. 1H NMR metabonomics indicates continued metabolic changes and sexual dimorphism post-parasite clearance in self-limiting murine malaria model.

    Arjun Sengupta

    Full Text Available Malaria, a mosquito-borne disease caused by Plasmodium spp. is considered to be a global threat, specifically for the developing countries. In human subjects considerable information exists regarding post-malarial physiology. However, most murine malarial models are lethal, and most studies deal with acute phases occurring as disease progresses. Much less is known regarding physiological status post-parasite clearance. We have assessed the physiological changes at the organ levels using (1H NMR based metabonomics in a non lethal self-clearing murine malarial model of P. chabaudi parasites and Balb/C, far beyond the parasite clearance point. The results showed distinct metabolic states between uninfected and infected mice at the peak parasitemia, as well as three weeks post-parasite clearance. Our data also suggests that the response at the peak infection as well as recovery exhibited distinct sexual dimorphism. Specifically, we observed accumulation of acetylcholine in the brain metabolic profile of both the sexes. This might have important implication in understanding the pathophysiology of the post malarial neurological syndromes. In addition, the female liver showed high levels of glucose, dimethylglycine, methylacetoacetate and histidine after three weeks post-parasite clearance, while the males showed accumulation of branched chain amino acids, lysine, glutamine and bile acids.

  4. Application of the indirect fluorescent antibody assay in the study of malaria infection in the Yangtze River Three Gorges Reservoir, China

    Xiang Zheng

    2009-08-01

    Full Text Available Abstract Background China Yangtze Three Gorges Project (TGP is one of the biggest construction projects in the world. The areas around the Three Gorge Dam has a history of tertian malaria and subtertian malaria epidemic, but there are no overall data about malaria epidemics before the completion of the project. The objective of this study was to get a reliable baseline on malaria infection in the Yangtze River Three Gorges reservoir area and to provide reference data for future studies about the impact of the project on malaria epidemics. Methods Two surveys of malaria infection were carried out in area, at six-month intervals in May and October 2008. About 3,600 dual specimens blood film samples for parasite diagnosis and filter paper blood spots for serology (using the immunofluorescence antibody test were collected from the general population, including school populations, whenever possible. Results The overall percentage of positive response of the same population during post-transmission periods was about twice (1.40/0.72 of that in pre-transmission. Positive individuals under 15 years of age were detected in all the localities. Conclusion A certain extent of malaria infection existed in this area. Additional studies are needed to determine the length of malaria experience, and chemotherapeutic intervention as well as the distribution of main vectors for transmission in this area.

  5. Synergistic Malaria Parasite Killing by Two Types of Plasmodial Surface Anion Channel Inhibitors.

    Margaret Pain

    Full Text Available Malaria parasites increase their host erythrocyte's permeability to a broad range of ions and organic solutes. The plasmodial surface anion channel (PSAC mediates this uptake and is an established drug target. Development of therapies targeting this channel is limited by several problems including interactions between known inhibitors and permeating solutes that lead to incomplete channel block. Here, we designed and executed a high-throughput screen to identify a novel class of PSAC inhibitors that overcome this solute-inhibitor interaction. These new inhibitors differ from existing blockers and have distinct effects on channel-mediated transport, supporting a model of two separate routes for solute permeation though PSAC. Combinations of inhibitors specific for the two routes had strong synergistic action against in vitro parasite propagation, whereas combinations acting on a single route produced only additive effects. The magnitude of synergism depended on external nutrient concentrations, consistent with an essential role of the channel in parasite nutrient acquisition. The identified inhibitors will enable a better understanding of the channel's structure-function and may be starting points for novel combination therapies that produce synergistic parasite killing.

  6. Malaria and HIV co-infection and their effect on haemoglobin levels ...

    EB

    Multivariable logistic regression analysis showed that patients with dual infection of malaria and HIV were ... AIDS in Nigeria4 and integrated control efforts are immeasurably ... malaria diagnosis was determined by a reddish chromatin dot ...

  7. Co-existence of malaria and urinary tract infection among children ...

    Co-existence of malaria and urinary tract infection among children under five: ... was the predominant cause of the UTI and the isolates were highly resistant ... Keywords: Malaria, UTI, antibiotic sensitivity pattern, parasitaemia, bacteriuria, fever ...

  8. Host control of malaria infections: constraints on immune and erythropoeitic response kinetics.

    Philip G McQueen

    2008-08-01

    Full Text Available The two main agents of human malaria, Plasmodium vivax and Plasmodium falciparum, can induce severe anemia and provoke strong, complex immune reactions. Which dynamical behaviors of host immune and erythropoietic responses would foster control of infection, and which would lead to runaway parasitemia and/or severe anemia? To answer these questions, we developed differential equation models of interacting parasite and red blood cell (RBC populations modulated by host immune and erythropoietic responses. The model immune responses incorporate both a rapidly responding innate component and a slower-responding, long-term antibody component, with several parasite developmental stages considered as targets for each type of immune response. We found that simulated infections with the highest parasitemia tended to be those with ineffective innate immunity even if antibodies were present. We also compared infections with dyserythropoiesis (reduced RBC production during infection to those with compensatory erythropoiesis (boosted RBC production or a fixed basal RBC production rate. Dyserythropoiesis tended to reduce parasitemia slightly but at a cost to the host of aggravating anemia. On the other hand, compensatory erythropoiesis tended to reduce the severity of anemia but with enhanced parasitemia if the innate response was ineffective. For both parasite species, sharp transitions between the schizont and the merozoite stages of development (i.e., with standard deviation in intra-RBC development time parasite development might help control parasitemia. Finally, our simulations suggest that P. vivax can induce severe anemia as readily as P. falciparum for the same type of immune response, though P. vivax attacks a much smaller subset of RBCs. Since most P. vivax infections are nonlethal (if debilitating clinically, this suggests that P

  9. Encapsulation of metalloporphyrins improves their capacity to block the viability of the human malaria parasite Plasmodium falciparum.

    Alves, Eduardo; Iglesias, Bernardo A; Deda, Daiana K; Budu, Alexandre; Matias, Tiago A; Bueno, Vânia B; Maluf, Fernando V; Guido, Rafael V C; Oliva, Glaucius; Catalani, Luiz H; Araki, Koiti; Garcia, Celia R S

    2015-02-01

    Several synthetic metallated protoporphyrins (M-PPIX) were tested for their ability to block the cell cycle of the lethal human malaria parasite Plasmodium falciparum. After encapsulating the porphyrin derivatives in micro- and nanocapsules of marine atelocollagen, their effects on cultures of red blood cells infected (RBC) with P. falciparum were verified. RBCs infected with synchronized P. falciparum incubated for 48 h showed a toxic effect over a micromolar range. Strikingly, the IC50 of encapsulated metalloporphyrins reached nanomolar concentrations, where Zn-PPIX showed the best antimalarial effect, with an IC50=330 nM. This value is an 80-fold increase in the antimalarial activity compared to the antimalarial effect of non-encapsulated Zn-PPIX. These findings reveal that the incubation of P. falciparum infected-RBCs with 20 μM Zn-PPIX reduced the size of hemozoin crystal by 34%, whereas a 28% reduction was noticed with chloroquine, confirming the importance of heme detoxification pathway in drug therapy. In this study, synthetic metalloporphyrins were tested as therapeutics that target Plasmodium falciparum. The IC50 of encapsulated metalloporphyrins was found to be in the nanomolar concentration range, with encapsulated Zn-PPIX showing an 80-fold increase in its antimalarial activity compared to the non-encapsulated form. Copyright © 2015. Published by Elsevier Inc.

  10. Parasite infection alters nitrogen cycling at the ecosystem scale.

    Mischler, John; Johnson, Pieter T J; McKenzie, Valerie J; Townsend, Alan R

    2016-05-01

    Despite growing evidence that parasites often alter nutrient flows through their hosts and can comprise a substantial amount of biomass in many systems, whether endemic parasites influence ecosystem nutrient cycling, and which nutrient pathways may be important, remains conjectural. A framework to evaluate how endemic parasites alter nutrient cycling across varied ecosystems requires an understanding of the following: (i) parasite effects on host nutrient excretion; (ii) ecosystem nutrient limitation; (iii) effects of parasite abundance, host density, host functional role and host excretion rate on nutrient flows; and (iv) how this infection-induced nutrient flux compares to other pools and fluxes. Pathogens that significantly increase the availability of a limiting nutrient within an ecosystem should produce a measurable ecosystem-scale response. Here, we combined field-derived estimates of trematode parasite infections in aquatic snails with measurements of snail excretion and tissue stoichiometry to show that parasites are capable of altering nutrient excretion in their intermediate host snails (dominant grazers). We integrated laboratory measurements of host nitrogen excretion with field-based estimates of infection in an ecosystem model and compared these fluxes to other pools and fluxes of nitrogen as measured in the field. Eighteen nitrogen-limited ponds were examined to determine whether infection had a measurable effect on ecosystem-scale nitrogen cycling. Because of their low nitrogen content and high demand for host carbon, parasites accelerated the rate at which infected hosts excreted nitrogen to the water column in a dose-response manner, thereby shifting nutrient stoichiometry and availability at the ecosystem scale. Infection-enhanced fluxes of dissolved inorganic nitrogen were similar to other commonly important environmental sources of bioavailable nitrogen to the system. Additional field measurements within nitrogen-limited ponds indicated that

  11. Long-term impact of childhood malaria infection on school performance among school children in a malaria endemic area along the Thai-Myanmar border.

    Vorasan, Nutchavadee; Pan-Ngum, Wirichada; Jittamala, Podjanee; Maneeboonyang, Wanchai; Rukmanee, Prasert; Lawpoolsri, Saranath

    2015-10-09

    Children represent a high-risk group for malaria worldwide. Among people in Thailand who have malaria during childhood, some may have multiple malaria attacks during their lifetime. Malaria may affect neurological cognition in children, resulting in short-term impairment of memory and language functions. However, little is known regarding the long-term effects of malaria infection on cognitive function. This study examines the long-term impact of malaria infection on school performance among school children living in a malaria-endemic area along the Thai-Myanmar border. A retrospective cohort study was conducted among school children aged 6-17 years in a primary-secondary school of a sub-district of Ratchaburi Province, Thailand. History of childhood malaria infection was obtained from the medical records of the sole malaria clinic in the area. School performance was assessed by using scores for the subjects Thai Language and Mathematics in 2014. Other variables, such as demographic characteristics, perinatal history, nutritional status, and emotional intelligence, were also documented. A total of 457 students were included, 135 (30 %) of whom had a history of uncomplicated malaria infection. About half of the malaria-infected children had suffered infection before the age of four years. The mean scores for both Mathematics and Thai Language decreased in relation to the increasing number of malaria attacks. Most students had their last malaria episode more than two years previously. The mean scores were not associated with duration since the last malaria attack. The association between malaria infection and school performance was not significant after adjusting for potential confounders, including gender, school absenteeism over a semester term, and emotional intelligence. This study characterizes the long-term consequences of uncomplicated malaria disease during childhood. School performance was not associated with a history of malaria infection, considering that

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

    Muregi, Francis W; Ohta, Isao; Masato, Uchijima; Kino, Hideto; Ishih, Akira

    2011-01-01

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

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

    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

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

    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.

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

    Rao, Pavitra N.; Santos, Jorge M.; Pain, Arnab; Templeton, Thomas J.; Mair, Gunnar R.

    2016-01-01

    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.

  16. The utility of screening for parasitic infections in HIV-1-infected Africans with eosinophilia in London.

    Sarner, Liat; Fakoya, Ade O; Tawana, Cheryl; Allen, Elizabeth; Copas, Andrew J; Chiodini, Peter L; Fenton, Kevin A

    2007-09-01

    The presence of asymptomatic eosinophilia in HIV patients has been demonstrated to have a wide variety of causes. Untreated parasitic infections in immunocompromised individuals can have potentially serious consequences. The utility of screening for parasitic infections in immigrant HIV-positive Africans with eosinophilia was investigated in a UK-based HIV clinic. HIV-positive African patients with eosinophilia were matched with HIV-positive African controls without eosinophilia. More than half of African HIV patients with eosinophilia had positive parasitic serology, and were significantly more likely to have positive serology compared with African HIV patients without eosinophilia. This study shows that asymptomatic eosinophilia in HIV-1-infected Africans is strongly suggestive of underlying parasitic infection. Individuals with eosinophilia should thus be screened for parasitic infections according to the infections prevalent in the countries they have lived in or visited for substantial periods of time.

  17. High prevalence of asymptomatic malaria infections: a cross-sectional study in rural areas in six departments in Haiti.

    Elbadry, Maha A; Al-Khedery, Basima; Tagliamonte, Massimiliano S; Yowell, Charles A; Raccurt, Christian P; Existe, Alexandre; Boncy, Jacques; Weppelmann, Thomas A; Beau De Rochars, Valery E M; Lemoine, Jean F; Okech, Bernard A; Dame, John B

    2015-12-21

    Public health measures are poised for transition from malaria control to malaria elimination on the island of Hispaniola. Assessment of the reservoir of asymptomatic infections from which acute malaria cases may derive is critical to plan and evaluate elimination efforts. Current field technology is ill suited for detecting sub-microscopic infections, thus highly sensitive survey methods capable of detecting virtually all infections are needed. In this study the prevalence of infection with Plasmodium falciparum was determined in patients seeking medical care primarily for non-febrile conditions in six departments in Haiti using a newly designed qRT-PCR-based assay. Three different methods of parasite detection were compared to assess their utility in approximating the prevalence of P. falciparum infections in the population: malaria rapid diagnostic test (RDT) designed to detect histidine-rich protein 2 (HRP2), thick smear microscopy, and a quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay based upon the small sub-unit ribosomal RNA. The limit of detection of the qRT-PCR assay utilized was 0.0003 parasite/µL of blood. Venous blood was obtained from a total of 563 subjects from six departments in Haiti, all of whom were seeking medical attention without complaints consistent with malaria. Each subject was questioned for knowledge and behaviour using demographic and epidemiological survey to identify risk factors for disease transmission. Among the 563 samples tested, ten and 16 were found positive for malaria by RDT and microscopy, respectively. Using the qRT-PCR test to assess the infection status of these subjects, an additional 92 were identified for a total of 108. Based upon the qRT-PCR assay results, a wide variation in prevalence of infection in asymptomatic subjects was seen between geographic locations ranging from 4-41%. The prevalence of infection was highest in the Grand Anse, Nord and Sud-Est Departments, and demographic

  18. Depletion of Plasmodium berghei Plasmoredoxin Reveals a Non-Essential Role for Life Cycle Progression of the Malaria Parasite

    Buchholz, Kathrin; Rahlfs, Stefan; Schirmer, R. Heiner; Becker, Katja; Matuschewski, Kai

    2008-01-01

    Proliferation of the pathogenic Plasmodium asexual blood stages in host erythrocytes requires an exquisite capacity to protect the malaria parasite against oxidative stress. This function is achieved by a complex antioxidant defence system composed of redox-active proteins and low MW antioxidants. Here, we disrupted the P. berghei plasmoredoxin gene that encodes a parasite-specific 22 kDa member of the thioredoxin superfamily. The successful generation of plasmoredoxin knockout mutants in the...

  19. Additional burden of asymptomatic and sub-patent malaria infections during low transmission season in forested tribal villages in Chhattisgarh, India.

    Chourasia, Mehul Kumar; Raghavendra, Kamaraju; Bhatt, Rajendra M; Swain, Dipak Kumar; Meshram, Hemraj M; Meshram, Jayant K; Suman, Shrity; Dubey, Vinita; Singh, Gyanendra; Prasad, Kona Madhavinadha; Kleinschmidt, Immo

    2017-08-08

    The burden of sub-patent malaria is difficult to recognize in low endemic areas due to limitation of diagnostic tools, and techniques. Polymerase chain reaction (PCR), a molecular based technique, is one of the key methods for detection of low parasite density infections. The study objective was to assess the additional burden of asymptomatic and sub-patent malaria infection among tribal populations inhabiting three endemic villages in Keshkal sub-district, Chhattisgarh, India. A cross-sectional survey was conducted in March-June 2016, during the low transmission season, to measure and compare prevalence of malaria infection using three diagnostics: rapid diagnostic test, microscopy and nested-PCR. Out of 437 individuals enrolled in the study, 103 (23.6%) were malaria positive by PCR and/or microscopy of whom 89.3% were Plasmodium falciparum cases, 77.7% were afebrile and 35.9% had sub-patent infections. A substantial number of asymptomatic and sub-patent malaria infections were identified in the survey. Hence, strategies for identifying and reducing the hidden burden of asymptomatic and sub-patent infections should focus on forest rural tribal areas using more sensitive molecular diagnostic methods to curtail malaria transmission.

  20. Use of buffy coat thick films in detecting malaria parasites in patients with negative conventional thick films.

    Duangdee, Chatnapa; Tangpukdee, Noppadon; Krudsood, Srivicha; Wilairatana, Polrat

    2012-04-01

    To determine the frequency of malaria parasite detection from the buffy coat blood films by using capillary tube in falciparum malaria patients with negative conventional thick films. Thirty six uncomplicated falciparum malaria patients confirmed by conventional thick and thin films were included in the study. The patients were treated with artemisinin combination therapy at Hospital for Tropical Diseases, Bangkok, Thailand for 28 day. Fingerpricks for conventional blood films were conducted every 6 hours until negative parasitemia, then daily fingerpricks for parasite checks were conducted until the patients were discharged from hospital. Blood samples were also concurrently collected in 3 heparinized capillary tubes at the same time of fingerpricks for conventional blood films when the prior parasitemia was negative on thin films and parasitemia was lower than 50 parasites/200 white blood cells by thick film. The first negative conventional thick films were compared with buffy coat thick films for parasite identification. Out of 36 patients with thick films showing negative for asexual forms of parasites, buffy coat films could detect remaining 10 patients (27.8%) with asexual forms of Plasmodium falciparum. The study shows that buffy coat thick films are useful and can detect malarial parasites in 27.8% of patients whose conventional thick films show negative parasitemia.

  1. Molecular inference of sources and spreading patterns of Plasmodium falciparum malaria parasites in internally displaced persons settlements in Myanmar-China border area.

    Lo, Eugenia; Zhou, Guofa; Oo, Winny; Lee, Ming-Chieh; Baum, Elisabeth; Felgner, Philip L; Yang, Zhaoqing; Cui, Liwang; Yan, Guiyun

    2015-07-01

    In Myanmar, civil unrest and establishment of internally displaced persons (IDP) settlement along the Myanmar-China border have impacted malaria transmission. The growing IDP populations raise deep concerns about health impact on local communities. Microsatellite markers were used to examine the source and spreading patterns of Plasmodium falciparum between IDP settlement and surrounding villages in Myanmar along the China border. Genotypic structure of P. falciparum was compared over the past three years from the same area and the demographic history was inferred to determine the source of recent infections. In addition, we examined if border migration is a factor of P. falciparum infections in China by determining gene flow patterns across borders. Compared to local community, the IDP samples showed a reduced and consistently lower genetic diversity over the past three years. A strong signature of genetic bottleneck was detected in the IDP samples. P. falciparum infections from the border regions in China were genetically similar to Myanmar and parasite gene flow was not constrained by geographical distance. Reduced genetic diversity of P. falciparum suggested intense malaria control within the IDP settlement. Human movement was a key factor to the spread of malaria both locally in Myanmar and across the international border. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Radioimmunoassays and related procedures in the diagnosis of parasitic infections

    Dessaint, J.P.; Cesbron, J.Y.; Lutsch, C.; Nogueira-Queiroz, J.A.; Capron, A.

    1986-01-01

    Immunological tests for the diagnosis of parasitic infections have long been used, yet the marked variability in seroreactivity of infected patients is still a challenge to immunoparasitologists. In the case of helminth parasites, especially schistosomes and filariae, immunoassays have benefited by numerous advances in the characterization and purification of antigens and by the use of monoclonal antibodies. The identification of functional antigens allows the detection of putative protective (or blocking) antibody responses by competitive RIAs using monoclonal antibodies in schistosomiasis. While progress has been made in the investigation of immunity in man, immunoassays for antibodies do not accurately correlate with parasite load, especially at lower antibody responses or after chemotherapy. Immunoassays for circulating parasite antigens have received much attention in recent years. Immunoradiometric assays and related procedures using infection sera or monoclonal antibodies are now being investigated in field conditions. Cross-reactions among circulating antigens from different parasites can decrease the specificity of such assays, whereas circulating immune complexes can interfere with the test. The recent use of RIAs to measure parasite antigens in the urine of patients with schistosomiasis or filariasis appears a promising approach. (author)

  3. Human parasitic protozoan infection to infertility: a systematic review.

    Shiadeh, Malihe Nourollahpour; Niyyati, Maryam; Fallahi, Shirzad; Rostami, Ali

    2016-02-01

    Protozoan parasitic diseases are endemic in many countries worldwide, especially in developing countries, where infertility is a major burden. It has been reported that such infections may cause infertility through impairment in male and female reproductive systems. We searched Medline, PubMed, and Scopus databases and Google scholar to identify the potentially relevant studies on protozoan parasitic infections and their implications in human and animal model infertility. Literature described that some of the protozoan parasites such as Trichomonas vaginalis may cause deformities of the genital tract, cervical neoplasia, and tubal and atypical pelvic inflammations in women and also non-gonoccocal urethritis, asthenozoospermia, and teratozoospermia in men. Toxopalasma gondii could cause endometritis, impaired folliculogenesis, ovarian and uterine atrophy, adrenal hypertrophy, vasculitis, and cessation of estrus cycling in female and also decrease in semen quality, concentration, and motility in male. Trypanosoma cruzi inhibits cell division in embryos and impairs normal implantation and development of placenta. Decrease in gestation rate, infection of hormone-producing glands, parasite invasion of the placenta, and overproduction of inflammatory cytokines in the oviducts and uterine horns are other possible mechanisms induced by Trypanosoma cruzi to infertility. Plasmodium spp. and Trypanosoma brucei spp. cause damage in pituitary gland, hormonal disorders, and decreased semen quality. Entamoeba histolytica infection leads to pelvic pain, salpingitis, tubo-ovarian abscess, and genital ulcers. Cutaneous and visceral leishmaniasis can induce genital lesion, testicular amyloidosis, inflammation of epididymis, prostatitis, and sperm abnormality in human and animals. In addition, some epidemiological studies have reported that rates of protozoan infections in infertile patients are higher than healthy controls. The current review indicates that protozoan parasitic

  4. The dangers of accepting a single diagnosis: case report of concurrent Plasmodium knowlesi malaria and dengue infection.

    Chong, Soon Eu; Mohamad Zaini, Rhendra Hardy; Suraiya, Siti; Lee, Kok Tong; Lim, Jo Anne

    2017-01-03

    Dengue and malaria are two common, mosquito-borne infections, which may lead to mortality if not managed properly. Concurrent infections of dengue and malaria are rare due to the different habitats of its vectors and activities of different carrier mosquitoes. The first case reported was in 2005. Since then, several concurrent infections have been reported between the dengue virus (DENV) and the malaria protozoans, Plasmodium falciparum and Plasmodium vivax. Symptoms of each infection may be masked by a simultaneous second infection, resulting in late treatment and severe complications. Plasmodium knowlesi is also a common cause of malaria in Malaysia with one of the highest rates of mortality. This report is one of the earliest in literature of concomitant infection between DENV and P. knowlesi in which a delay in diagnosis had placed a patient in a life-threatening situation. A 59-year old man staying near the Belum-Temengor rainforest at the Malaysia-Thailand border was admitted with fever for 6 days, with respiratory distress. His non-structural protein 1 antigen and Anti-DENV Immunoglobulin M tests were positive. He was treated for severe dengue with compensated shock. Treating the dengue had so distracted the clinicians that a blood film for the malaria parasite was not done. Despite aggressive supportive treatment in the intensive care unit (ICU), the patient had unresolved acidosis as well as multi-organ failure involving respiratory, renal, liver, and haematological systems. It was due to the presentation of shivering in the ICU, that a blood film was done on the second day that revealed the presence of P. knowlesi with a parasite count of 520,000/μL. The patient was subsequently treated with artesunate-doxycycline and made a good recovery after nine days in ICU. This case contributes to the body of literature on co-infection between DENV and P. knowlesi and highlights the clinical consequences, which can be severe. Awareness should be raised among

  5. Population genomic structure and adaptation in the zoonotic malaria parasite Plasmodium knowlesi

    Assefa, Samuel

    2015-10-06

    Malaria cases caused by the zoonotic parasite Plasmodium knowlesi are being increasingly reported throughout Southeast Asia and in travelers returning from the region. To test for evidence of signatures of selection or unusual population structure in this parasite, we surveyed genome sequence diversity in 48 clinical isolates recently sampled from Malaysian Borneo and in five lines maintained in laboratory rhesus macaques after isolation in the 1960s from Peninsular Malaysia and the Philippines. Overall genomewide nucleotide diversity (π = 6.03 × 10) was much higher than has been seen in worldwide samples of either of the major endemic malaria parasite species Plasmodium falciparum and Plasmodium vivax. A remarkable substructure is revealed within P. knowlesi, consisting of two major sympatric clusters of the clinical isolates and a third cluster comprising the laboratory isolates. There was deep differentiation between the two clusters of clinical isolates [mean genomewide fixation index (F) = 0.21, with 9,293 SNPs having fixed differences of F = 1.0]. This differentiation showed marked heterogeneity across the genome, with mean F values of different chromosomes ranging from 0.08 to 0.34 and with further significant variation across regions within several chromosomes. Analysis of the largest cluster (cluster 1, 38 isolates) indicated long-term population growth, with negatively skewed allele frequency distributions (genomewide average Tajima\\'s D = -1.35). Against this background there was evidence of balancing selection on particular genes, including the circumsporozoite protein (csp) gene, which had the top Tajima\\'s D value (1.57), and scans of haplotype homozygosity implicate several genomic regions as being under recent positive selection.

  6. Population genomic structure and adaptation in the zoonotic malaria parasite Plasmodium knowlesi

    Assefa, Samuel; Lim, Caeul; Preston, Mark D.; Duffy, Craig W.; Nair, Mridul; Adroub, Sabir; Kadir, Khamisah A.; Goldberg, Jonathan M.; Neafsey, Daniel E.; Divis, Paul; Clark, Taane G.; Duraisingh, Manoj T.; Conway, David J.; Pain, Arnab; Singh, Balbir

    2015-01-01

    Malaria cases caused by the zoonotic parasite Plasmodium knowlesi are being increasingly reported throughout Southeast Asia and in travelers returning from the region. To test for evidence of signatures of selection or unusual population structure in this parasite, we surveyed genome sequence diversity in 48 clinical isolates recently sampled from Malaysian Borneo and in five lines maintained in laboratory rhesus macaques after isolation in the 1960s from Peninsular Malaysia and the Philippines. Overall genomewide nucleotide diversity (π = 6.03 × 10) was much higher than has been seen in worldwide samples of either of the major endemic malaria parasite species Plasmodium falciparum and Plasmodium vivax. A remarkable substructure is revealed within P. knowlesi, consisting of two major sympatric clusters of the clinical isolates and a third cluster comprising the laboratory isolates. There was deep differentiation between the two clusters of clinical isolates [mean genomewide fixation index (F) = 0.21, with 9,293 SNPs having fixed differences of F = 1.0]. This differentiation showed marked heterogeneity across the genome, with mean F values of different chromosomes ranging from 0.08 to 0.34 and with further significant variation across regions within several chromosomes. Analysis of the largest cluster (cluster 1, 38 isolates) indicated long-term population growth, with negatively skewed allele frequency distributions (genomewide average Tajima's D = -1.35). Against this background there was evidence of balancing selection on particular genes, including the circumsporozoite protein (csp) gene, which had the top Tajima's D value (1.57), and scans of haplotype homozygosity implicate several genomic regions as being under recent positive selection.

  7. Laboratory diagnostics of malaria

    Siahaan, L.

    2018-03-01

    Even now, malaria treatment should only be administered after laboratory confirmation. There are several principal methods for diagnosing malaria. All these methods have their disadvantages.Presumptive treatment of malaria is widely practiced where laboratory tests are not readily available. Microscopy of Giemsa-stained thick and thin blood films remains the gold standard for the diagnosis of malaria infection. The technique of slide preparation, staining and reading are well known and standardized, and so is the estimate of the parasite density and parasite stages. Microscopy is not always available or feasible at primary health services in limited resource settings due to cost, lack of skilled manpower, accessories and reagents required. Rapid diagnostic tests (RDTs) are potential tools for parasite-based diagnosis since the tests are accurate in detecting malaria infections and are easy to use. The test is based on the capture of parasite antigen that released from parasitized red blood cells using monoclonal antibodies prepared against malaria antigen target. Polymerase Chain Reaction (PCR), depend on DNA amplification approaches and have higher sensitivity than microscopy. PCR it is not widely used due to the lack of a standardized methodology, high costs, and the need for highly-trained staff.

  8. Antibodies from malaria-exposed pregnant women recognize trypsin resistant epitopes on the surface of Plasmodium falciparum-infected erythrocytes selected for adhesion to chondroitin sulphate A

    Sharling, Lisa; Enevold, Anders; Sowa, Kordai M P

    2004-01-01

    of CSA binding and surface recognition of CSA selected parasites by serum IgG from malaria exposed pregnant women. Thus, the complete molecular definition of an antigenic P. falciparum erythrocyte surface protein that can be used as a malaria in pregnancy vaccine has not yet been achieved.......-specific antibodies induced as a result of pregnancy associated malaria (PAM). METHODS: Fluorescence activated cell sorting (FACS) was used to measure the levels of adult Scottish and Ghanaian male, and Ghanaian pregnant female plasma immunoglobulin G (IgG) that bind to the surface of infected erythrocytes. P....... falciparum infected erythrocytes selected for adhesion to CSA were found to express trypsin-resistant VSA that are the target of naturally acquired antibodies from pregnant women living in a malaria endemic region of Ghana. However in vitro adhesion to CSA and HA was relatively trypsin sensitive. An improved...

  9. A plant-like proton-pump partnership in the malaria parasite

    Allen, R.J.W.; Saliba, K.J.; Zissis, S.; Kirk, K.

    2001-01-01

    Full text: The 'intraerythrocytic' form of the human malaria parasite. Plasmodium falciparum contains an acidic 'digestive vacuole' which is believed to be the main site of haemoglobin degradation, and the major site of action of many antimalarial drugs. The mechanism/s by which this organelle is acidified have not been investigated. In plant cells, the internal acidic vacuole has on its membrane two types of H + -pumps which contribute to the generation of an acidic pH: a vacuolar-type H + -ATPase (V-H + -ATPase) and a vacuolar H + -pyrophosphatase (V-H + -PPase). The presence of a V-H + -ATPase on the digestive vacuole membrane of P. falciparum has been demonstrated by immuno-electron microscopy (J. Biol. Chem. (2000) 275: 34353-34358) but its functional activity on this organelle has not been demonstrated. Two V-H + -PPase genes have been shown to be expressed in the intraerythrocytic stage of the P. falciparum parasite (Mol. Biochem. Parasitol. (2001) 114: 183-195); however, immunological methods failed to detect either on the parasite digestive vacuole. In this study we use a combination of NMR spectroscopy and fluorescence techniques to show that (i) P. falciparum contains low levels of pyrophosphate, and (ii) that both ATP and pyrophosphate are able to energise the acidification of the parasite's digestive vacuole. We propose that, like many plant cells the digestive vacuole of P. falciparum parasites has, on its membrane, a V-H + -PPase as well as a V-H + -ATPaSe, and that both pumps contribute to the pH regulation of this organelle

  10. A plant-like proton-pump partnership in the malaria parasite

    Allen, R J.W.; Saliba, K J; Zissis, S; Kirk, K [Australian National University, ACT (Australia)

    2001-07-01

    Full text: The 'intraerythrocytic' form of the human malaria parasite. Plasmodium falciparum contains an acidic 'digestive vacuole' which is believed to be the main site of haemoglobin degradation, and the major site of action of many antimalarial drugs. The mechanism/s by which this organelle is acidified have not been investigated. In plant cells, the internal acidic vacuole has on its membrane two types of H{sup +}-pumps which contribute to the generation of an acidic pH: a vacuolar-type H{sup +}-ATPase (V-H{sup +}-ATPase) and a vacuolar H{sup +}-pyrophosphatase (V-H{sup +}-PPase). The presence of a V-H{sup +}-ATPase on the digestive vacuole membrane of P. falciparum has been demonstrated by immuno-electron microscopy (J. Biol. Chem. (2000) 275: 34353-34358) but its functional activity on this organelle has not been demonstrated. Two V-H{sup +}-PPase genes have been shown to be expressed in the intraerythrocytic stage of the P. falciparum parasite (Mol. Biochem. Parasitol. (2001) 114: 183-195); however, immunological methods failed to detect either on the parasite digestive vacuole. In this study we use a combination of NMR spectroscopy and fluorescence techniques to show that (i) P. falciparum contains low levels of pyrophosphate, and (ii) that both ATP and pyrophosphate are able to energise the acidification of the parasite's digestive vacuole. We propose that, like many plant cells the digestive vacuole of P. falciparum parasites has, on its membrane, a V-H{sup +}-PPase as well as a V-H{sup +}-ATPaSe, and that both pumps contribute to the pH regulation of this organelle.

  11. The Cytoplasmic Prolyl-tRNA Synthetase of the Malaria Parasite is a Dual-Stage Target for Drug Development

    Herman, Jonathan D.; Pepper, Lauren R.; Cortese, Joseph F.; Estiu, Guillermina; Galinsky, Kevin; Zuzarte-Luis, Vanessa; Derbyshire, Emily R.; Ribacke, Ulf; Lukens, Amanda K.; Santos, Sofia A.; Patel, Vishal; Clish, Clary B.; Sullivan, William J.; Zhou, Huihao; Bopp, Selina E.; Schimmel, Paul; Lindquist, Susan; Clardy, Jon; Mota, Maria M.; Keller, Tracy L.; Whitman, Malcolm; Wiest, Olaf; Wirth, Dyann F.; Mazitschek, Ralph

    2015-01-01

    The emergence of drug resistance is a major limitation of current antimalarials. The discovery of new druggable targets and pathways including those that are critical for multiple life cycle stages of the malaria parasite is a major goal for the development of the next-generation of antimalarial drugs. Using an integrated chemogenomics approach that combined drug-resistance selection, whole genome sequencing and an orthogonal yeast model, we demonstrate that the cytoplasmic prolyl-tRNA synthetase (PfcPRS) of the malaria parasite Plasmodium falciparum is a biochemical and functional target of febrifugine and its synthetic derivatives such as halofuginone. Febrifugine is the active principle of a traditional Chinese herbal remedy for malaria. We show that treatment with febrifugine derivatives activated the amino acid starvation response in both P. falciparum and a transgenic yeast strain expressing PfcPRS. We further demonstrate in the P. berghei mouse model of malaria that halofuginol, a new halofuginone analog that we developed, is highly active against both liver and asexual blood stages of the malaria parasite. Halofuginol, unlike halofuginone and febrifugine, is well tolerated at efficacious doses, and represents a promising lead for the development of dual-stage next generation antimalarials. PMID:25995223

  12. Role of parasites in cancer.

    Mandong, B M; Ngbea, J A; Raymond, Vhriterhire

    2013-01-01

    In areas of parasitic endemicity, the occurrence of cancer that is not frequent may be linked with parasitic infection. Epidemiological correlates between some parasitic infections and cancer is strong, suggesting a strong aetiological association. The common parasites associated with human cancers are schistosomiasis, malaria, liver flukes (Clonorchis sinenses, Opistorchis viverrini). To review the pathology, literature and methods of diagnosis. Literature review from peer reviewed Journals cited in PubMed and local journals. Parasites may serve as promoters of cancer in endemic areas of infection.

  13. Parasitic Infections among Restaurant Workers in Mukalla (Hadhramout/Yemen

    AM AL-Haddad

    2008-09-01

    Full Text Available "nBackground: To identify intestinal parasites among restaurant workers in Mukalla, Yemen in 2007."nMethods: Stool specimens were collected and examined from a total of 500 restaurant workers at Hadhramout University Health Center .Three types of techniques were used: direct examination, saline sedimentation and formol-ether concentration."nResults:  The positivity in majority of them was single infection whereas 6 cases were double infection that constituted 1.3% of the prevalence. The prevalence was 14.8 % for Entamoeba histolytica/dispor, and 5.2 % for Giardia lamblia, while it was 4.4% for Hymenolepis nana. Other intestinal parasites including Ascaris lumbricoides, Ancylostoma duodinale were also detected. Additionally, the blood parasite Schistosoma mansoni was also detected in 4 cases. The double infection was only with E. histolytica/dispor and Giardia. The infection with these parasites was also accompanied by abdominal troubles "diarrhea, constipation", nausea and vomiting."nConclusion:  These results lead to understand that sanitary measurements are not effective, and this hazardous situation facilitate parasitic agents' distribution among clients. The effectiveness of current pre-employment screening policy must be annual and systematic surveillance is needed in addition to health education.

  14. The Clp Chaperones and Proteases of the Human Malaria Parasite Plasmodium falciparum

    Bakkouri, Majida El; Pow, Andre; Mulichak, Anne; Cheung, Kevin L.Y.; Artz, Jennifer D.; Amani, Mehrnaz; Fell, Stuart; de Koning-Ward, Tania F.; Goodman, C. Dean; McFadden, Geoffrey I.; Ortega, Joaquin; Hui, Raymond; Houry, Walid A. (McMaster U.); (Melbourne); (Toronto); (Deakin); (HWMRI)

    2015-02-09

    The Clp chaperones and proteases play an important role in protein homeostasis in the cell. They are highly conserved across prokaryotes and found also in the mitochondria of eukaryotes and the chloroplasts of plants. They function mainly in the disaggregation, unfolding and degradation of native as well as misfolded proteins. Here, we provide a comprehensive analysis of the Clp chaperones and proteases in the human malaria parasite Plasmodium falciparum. The parasite contains four Clp ATPases, which we term PfClpB1, PfClpB2, PfClpC and PfClpM. One PfClpP, the proteolytic subunit, and one PfClpR, which is an inactive version of the protease, were also identified. Expression of all Clp chaperones and proteases was confirmed in blood-stage parasites. The proteins were localized to the apicoplast, a non-photosynthetic organelle that accommodates several important metabolic pathways in P. falciparum, with the exception of PfClpB2 (also known as Hsp101), which was found in the parasitophorous vacuole. Both PfClpP and PfClpR form mostly homoheptameric rings as observed by size-exclusion chromatography, analytical ultracentrifugation and electron microscopy. The X-ray structure of PfClpP showed the protein as a compacted tetradecamer similar to that observed for Streptococcus pneumoniae and Mycobacterium tuberculosis ClpPs. Our data suggest the presence of a ClpCRP complex in the apicoplast of P. falciparum.

  15. Enteric parasitic infections in HIV-infected patients with low CD4 counts in Toto, Nigeria

    Abaver, D.T.; Nwobegahay, J.M.; Goon, D.T.; Khoza, L.B

    2012-01-01

    Objectives: Enteric parasites are a major cause of diarrhoea in HIV/AIDS patients with low CD4 counts. Parasitic infections in HIV-infected individuals can reduce their quality of life and life span, especially those who are severely immunosuppressed with a CD4 T-lymphocyte count 0.05). Conclusions: Low CD4 counts in HIV-infected patients can lead to enteric infections. This information strengthens the importance of monitoring CD4 counts and intestinal parasites. Routine CD4 testing will greatly improve the prognosis of HIV positive patients. (author)

  16. The Performance of a Rapid Diagnostic Test in Detecting Malaria Infection in Pregnant Women and the Impact of Missed Infections

    Williams, John E.; Cairns, Matthew; Njie, Fanta; Laryea Quaye, Stephen; Awine, Timothy; Oduro, Abraham; Tagbor, Harry; Bojang, Kalifa; Magnussen, Pascal; ter Kuile, Feiko O.; Woukeu, Arouna; Milligan, Paul; Chandramohan, Daniel; Greenwood, Brian

    2016-01-01

    Intermittent screening and treatment in pregnancy (ISTp) is a potential strategy for the control of malaria during pregnancy. However, the frequency and consequences of malaria infections missed by a rapid diagnostic test (RDT) for malaria are a concern. Primigravidae and secundigravidae who

  17. Global issues in allergy and immunology: Parasitic infections and allergy.

    Cruz, Alvaro A; Cooper, Philip J; Figueiredo, Camila A; Alcantara-Neves, Neuza M; Rodrigues, Laura C; Barreto, Mauricio L

    2017-11-01

    Allergic diseases are on the increase globally in parallel with a decrease in parasitic infection. The inverse association between parasitic infections and allergy at an ecological level suggests a causal association. Studies in human subjects have generated a large knowledge base on the complexity of the interrelationship between parasitic infection and allergy. There is evidence for causal links, but the data from animal models are the most compelling: despite the strong type 2 immune responses they induce, helminth infections can suppress allergy through regulatory pathways. Conversely, many helminths can cause allergic-type inflammation, including symptoms of "classical" allergic disease. From an evolutionary perspective, subjects with an effective immune response against helminths can be more susceptible to allergy. This narrative review aims to inform readers of the most relevant up-to-date evidence on the relationship between parasites and allergy. Experiments in animal models have demonstrated the potential benefits of helminth infection or administration of helminth-derived molecules on chronic inflammatory diseases, but thus far, clinical trials in human subjects have not demonstrated unequivocal clinical benefits. Nevertheless, there is sufficiently strong evidence to support continued investigation of the potential benefits of helminth-derived therapies for the prevention or treatment of allergic and other inflammatory diseases. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  18. Variation in apoptosis mechanisms employed by malaria parasites: the roles of inducers, dose dependence and parasite stages

    Matthews Holly

    2012-08-01

    , mitochondrial membrane potential remained intact. No relationship between ookinete density and apoptosis was detected but nutrient depletion significantly increased the proportion of ookinetes with chromatin condensation in four hours. Conclusions It is proposed that both a mitochondrial and an amitochondrial apoptotic pathway may be involved, dependent upon the trigger that induces apoptosis, and that pathways may differ between erythrocytic stages and ookinetes, or between rodent and human malaria parasites.

  19. The guanylhydrazone CNI-1493: an inhibitor with dual activity against malaria-inhibition of host cell pro-inflammatory cytokine release and parasitic deoxyhypusine synthase.

    Specht, Sabine; Sarite, Salem Ramadan; Hauber, Ilona; Hauber, Joachim; Görbig, Ulf F; Meier, Chris; Bevec, Dorian; Hoerauf, Achim; Kaiser, Annette

    2008-05-01

    Malaria is still a major cause of death in the tropics. There is an urgent need for new anti-malarial drugs because drug-resistant plasmodia frequently occur. Over recent years, we elucidated the biosynthesis of hypusine, a novel amino acid contained in eukaryotic initiation factor 5A (eIF-5A) in Plasmodium. Hypusine biosynthesis involves catalysis of deoxyhypusine synthase (DHS) in the first step of post-translational modification. In a screen for new inhibitors of purified plasmodium DHS, CNI-1493, a novel selective pro-inflammatory cytokine inhibitor used in clinical phase II for the treatment of Crohn's disease, inhibited the enzyme of the parasite 3-fold at a concentration of 2 microM. In vitro experiments with 200 microM CNI-1493 in Plasmodium-infected erythrocytes, which lack nuclei and DHS protein, showed a parasite clearance within 2 days. This can presumably be attributed to an anti-proliferating effect because of the inhibition of DHS by the parasite. The determined IC50 of CNI-1493 was 135.79 microM after 72 h. In vivo application of this substance in Plasmodium berghei ANKA-infected C57BL/6 mice significantly reduced parasitemia after dosage of 1 mg/kg or 4 mg/kg/body weight and prevented death of mice with cerebral malaria. This effect was paralleled by a decrease in serum TNF levels of the mice. We suggest that the new mechanism of CNI-1493 is caused by a decrease in modified eIF-5A biosynthesis with a downstream effect on the TNF synthesis of the host. From the current data, we consider CNI-1493 to be a promising drug for anti-malarial therapy because of its combined action, i.e., the decrease in eIF-5A biosynthesis of the parasite and host cell TNF biosynthesis.

  20. Depletion of Plasmodium berghei plasmoredoxin reveals a non-essential role for life cycle progression of the malaria parasite.

    Buchholz, Kathrin; Rahlfs, Stefan; Schirmer, R Heiner; Becker, Katja; Matuschewski, Kai

    2008-06-25

    Proliferation of the pathogenic Plasmodium asexual blood stages in host erythrocytes requires an exquisite capacity to protect the malaria parasite against oxidative stress. This function is achieved by a complex antioxidant defence system composed of redox-active proteins and low MW antioxidants. Here, we disrupted the P. berghei plasmoredoxin gene that encodes a parasite-specific 22 kDa member of the thioredoxin superfamily. The successful generation of plasmoredoxin knockout mutants in the rodent model malaria parasite and phenotypic analysis during life cycle progression revealed a non-vital role in vivo. Our findings suggest that plasmoredoxin fulfils a specialized and dispensable role for Plasmodium and highlights the need for target validation to inform drug development strategies.

  1. Malaria-infected female collared flycatchers (Ficedula albicollis do not pay the cost of late breeding.

    Katarzyna Kulma

    Full Text Available Life-history theory predicts that the trade-off between parasite defense and other costly traits such as reproduction may be most evident when resources are scarce. The strength of selection that parasites inflict on their host may therefore vary across environmental conditions. Collared flycatchers (Ficedula albicollis breeding on the Swedish island Öland experience a seasonal decline in their preferred food resource, which opens the possibility to test the strength of life-history trade-offs across environmental conditions. We used nested-PCR and quantitative-PCR protocols to investigate the association of Haemosporidia infection with reproductive performance of collared flycatcher females in relation to a seasonal change in the external environment. We show that despite no difference in mean onset of breeding, infected females produced relatively more of their fledglings late in the season. This pattern was also upheld when considering only the most common malaria lineage (hPHSIB1, however there was no apparent link between the reproductive output and the intensity of infection. Infected females produced heavier-than-average fledglings with higher-than-expected recruitment success late in the season. This reversal of the typical seasonal trend in reproductive output compensated them for lower fledging and recruitment rates compared to uninfected birds earlier in the season. Thus, despite different seasonal patterns of reproductive performance the overall number of recruits was the same for infected versus uninfected birds. A possible explanation for our results is that infected females breed in a different microhabitat where food availability is higher late in the season but also is the risk of infection. Thus, our results suggest that another trade-off than the one we aimed to test is more important for explaining variation in reproductive performance in this natural population: female flycatchers appear to face a trade-off between the risk

  2. Common dietary flavonoids inhibit the growth of the intraerythrocytic malaria parasite

    Saliba Kevin J

    2008-06-01

    Full Text Available Abstract Background Flavonoids are abundant plant phenolic compounds. More than 6000 have been identified to date, and some have been shown to possess antiparasitic activity. Here we investigate the effects of a range of common dietary flavonoids on the growth of two strains of the human malaria parasite Plasmodium falciparum. Findings A chloroquine-sensitive (3D7 and a chloroquine-resistant (7G8 strain of P. falciparum were tested for in vitro susceptibility to a range of individual dietary flavonoids and flavonoid combinations. Parasite susceptibility was measured in 96-well plates over 96 h using a previously described [3H]hypoxanthine incorporation assay. Of the eleven flavonoids tested, eight showed antiplasmodial activity against the 3D7 strain (with IC50 values between 11 and 66 μM, and all showed activity against the 7G8 strain (with IC50 values between 12 and 76 μM. The most active compound against both strains was luteolin, with IC50 values of 11 ± 1 μM and 12 ± 1 μM for 3D7 and 7G8, respectively. Luteolin was found to prevent the progression of parasite growth beyond the young trophozoite stage, and did not affect parasite susceptibility to the antimalarial drugs chloroquine or artemisinin. Combining low concentrations of flavonoids was found to produce an apparent additive antiplasmodial effect. Conclusion Certain common dietary flavonoids inhibit the intraerythrocytic growth of the 3D7 and 7G8 strains of P. falciparum. Flavonoid combinations warrant further investigation as antiplasmodial agents.

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

    Henrique Borges da Silva

    2015-02-01

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

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

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

    2015-02-01

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

  5. The Malaria Parasite Cyclin H Homolog PfCyc1 Is Required for Efficient Cytokinesis in Blood-Stage Plasmodium falciparum.

    Robbins, Jonathan A; Absalon, Sabrina; Streva, Vincent A; Dvorin, Jeffrey D

    2017-06-13

    All well-studied eukaryotic cell cycles are driven by cyclins, which activate cyclin-dependent kinases (CDKs), and these protein kinase complexes are viable drug targets. The regulatory control of the Plasmodium falciparum cell division cycle remains poorly understood, and the roles of the various CDKs and cyclins remain unclear. The P. falciparum genome contains multiple CDKs, but surprisingly, it does not contain any sequence-identifiable G 1 -, S-, or M-phase cyclins. We demonstrate that P. falciparum Cyc1 (PfCyc1) complements a G 1 cyclin-depleted Saccharomyces cerevisiae strain and confirm that other identified malaria parasite cyclins do not complement this strain. PfCyc1, which has the highest sequence similarity to the conserved cyclin H, cannot complement a temperature-sensitive yeast cyclin H mutant. Coimmunoprecipitation of PfCyc1 from P. falciparum parasites identifies PfMAT1 and PfMRK as specific interaction partners and does not identify PfPK5 or other CDKs. We then generate an endogenous conditional allele of PfCyc1 in blood-stage P. falciparum using a destabilization domain (DD) approach and find that PfCyc1 is essential for blood-stage proliferation. PfCyc1 knockdown does not impede nuclear division, but it prevents proper cytokinesis. Thus, we demonstrate that PfCyc1 has a functional divergence from bioinformatic predictions, suggesting that the malaria parasite cell division cycle has evolved to use evolutionarily conserved proteins in functionally novel ways. IMPORTANCE Human infection by the eukaryotic parasite Plasmodium falciparum causes malaria. Most well-studied eukaryotic cell cycles are driven by cyclins, which activate cyclin-dependent kinases (CDKs) to promote essential cell division processes. Remarkably, there are no identifiable cyclins that are predicted to control the cell cycle in the malaria parasite genome. Thus, our knowledge regarding the basic mechanisms of the malaria parasite cell cycle remains unsatisfactory. We

  6. Expression, characterization, and cellular localization of knowpains, papain-like cysteine proteases of the Plasmodium knowlesi malaria parasite.

    Rajesh Prasad

    Full Text Available Papain-like cysteine proteases of malaria parasites degrade haemoglobin in an acidic food vacuole to provide amino acids for intraerythrocytic parasites. These proteases are potential drug targets because their inhibitors block parasite development, and efforts are underway to develop chemotherapeutic inhibitors of these proteases as the treatments for malaria. Plasmodium knowlesi has recently been shown to be an important human pathogen in parts of Asia. We report expression and characterization of three P. knowlesi papain-like proteases, termed knowpains (KP2-4. Recombinant knowpains were produced using a bacterial expression system, and tested for various biochemical properties. Antibodies against recombinant knowpains were generated and used to determine their cellular localization in parasites. Inhibitory effects of the cysteine protease inhibitor E64 were assessed on P. knowlesi culture to validate drug target potential of knowpains. All three knowpains were present in the food vacuole, active in acidic pH, and capable of degrading haemoglobin at the food vacuolar pH (≈5.5, suggesting roles in haemoglobin degradation. The proteases showed absolute (KP2 and KP3 to moderate (KP4 preference for peptide substrates containing leucine at the P2 position; KP4 preferred arginine at the P2 position. While the three knowpains appear to have redundant roles in haemoglobin degradation, KP4 may also have a role in degradation of erythrocyte cytoskeleton during merozoite egress, as it displayed broad substrate specificity and was primarily localized at the parasite periphery. Importantly, E64 blocked erythrocytic development of P. knowlesi, with enlargement of food vacuoles, indicating inhibition of haemoglobin hydrolysis and supporting the potential for inhibition of knowpains as a strategy for the treatment of malaria. Functional expression and characterization of knowpains should enable simultaneous screening of available cysteine protease

  7. A scalable pipeline for highly effective genetic modification of a malaria parasite

    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.

  8. A scalable pipeline for highly effective genetic modification of a malaria parasite

    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

    2011-01-01

    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.

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

    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...

  10. Malaria and Vascular Endothelium

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

    2014-08-15

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

  11. Malaria and Vascular Endothelium

    Alencar, Aristóteles Comte Filho de; Lacerda, Marcus Vinícius Guimarães de; Okoshi, Katashi; Okoshi, Marina Politi

    2014-01-01

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

  12. Prevalence and intensity of intestinal parasitic infections and factors ...

    The factors established to be independently associated with presence of intestinal parasitic infection were: age 11-15 years P<0.001, use of plain water for hand washing P<0.05, eating food without spoon P<0.05, consuming raw vegetables P<0.001, untrimmed finger nails P<0.001 and source of drinking water [river ...

  13. Anaemia, Nutritional Status and Parasitic Infection among Preschool ...

    Objective: This study was carried out to determine the packed cell volume nutritional status and parasitic infection among preschool children living in rural villages. Subjects and Methods: A total of 116 preschool children in nine villages formed the population for this study. The preschool children were studied using ...

  14. Geophagy and parasitic infections in pregnant women attending an ...

    Background: Geophagy, a regular and deliberate habit of eating non-food substances is practiced worldwide and in sub-Saharan Africa. ... was not associated with parasitic infections in pregnant women, geophagy was found to have a significant association with education, history of geophagy and the feeding problems.

  15. Parasitic infections of anurans from an urbanized rainforest biotope ...

    The parasitic infections of anurans in an urbanized rainforest biotope in the Diobu, Port Harcourt area of Rivers State were investigated. The few anuran species encountered included Afrixalus fulvovittatus, Amietophrynus regularis, A. cameroonensis, Hyperolius concolor phase B, Hyperolius concolor phase C, ...

  16. Intestinal parasitic infections and the level of immunosuppression in ...

    Background: Opportunistic and non-opportunistic intestinal parasites play a significant role in the morbidity and mortality of HIV/AIDS-infected patients. The frequency of their occurrence strongly correlates with the patient's level of immunity. The most ..... Conflict of interest: Authors declare that they have no conflict of interest.

  17. Survey of gastrointestinal parasite infection in African lion ( Panthera ...

    Little is known about gastrointestinal parasite infections in large carnivores in Africa and what is available is largely from East Africa. We collected faecal samples from nine spotted hyaenas (Crocuta crocuta), 15 lions (Panthera leo) and 13 African wild dog (Lycaon pictus) from Luangwa Valley, Zambia. The most common ...

  18. HIV and parasitic co-infections in tuberculosis patients

    Range, N.; Magnussen, Pascal; Mugomela, A.

    2007-01-01

    A cross-sectional study was conducted in Mwanza, Tanzania, to determine the burden of HIV and parasitic co-infections among patients who were confirmed or suspected cases of pulmonary tuberculosis (PTB). Of the 655 patients investigated, 532 (81.2%) had been confirmed as PTB cases, by microscopy...

  19. Long- and short-term selective forces on malaria parasite genomes

    Nygaard, Sanne

    2010-09-09

    Plasmodium parasites, the causal agents of malaria, result in more than 1 million deaths annually. Plasmodium are unicellular eukaryotes with small ~23 Mb genomes encoding ~5200 protein-coding genes. The protein-coding genes comprise about half of these genomes. Although evolutionary processes have a significant impact on malaria control, the selective pressures within Plasmodium genomes are poorly understood, particularly in the non-protein-coding portion of the genome. We use evolutionary methods to describe selective processes in both the coding and non-coding regions of these genomes. Based on genome alignments of seven Plasmodium species, we show that protein-coding, intergenic and intronic regions are all subject to purifying selection and we identify 670 conserved non-genic elements. We then use genome-wide polymorphism data from P. falciparum to describe short-term selective processes in this species and identify some candidate genes for balancing (diversifying) selection. Our analyses suggest that there are many functional elements in the non-genic regions of these genomes and that adaptive evolution has occurred more frequently in the protein-coding regions of the genome. © 2010 Nygaard et al.

  20. Using green fluorescent malaria parasites to screen for permissive vector mosquitoes

    Martin Beatrice

    2006-03-01

    Full Text Available Abstract Background The Plasmodium species that infect rodents, particularly Plasmodium berghei and Plasmodium yoelii, are useful to investigate host-parasite interactions. The mosquito species that act as vectors of human plasmodia in South East Asia, Africa and South America show different susceptibilities to infection by rodent Plasmodium species. P. berghei and P. yoelii infect both Anopheles gambiae and Anopheles stephensi, which are found mainly in Africa and Asia, respectively. However, it was reported that P. yoelii can infect the South American mosquito, Anopheles albimanus, while P. berghei cannot. Methods P. berghei lines that express the green fluorescent protein were used to screen for mosquitoes that are susceptible to infection by P. berghei. Live mosquitoes were examined and screened for the presence of a fluorescent signal in the abdomen. Infected mosquitoes were then examined by time-lapse microscopy to reveal the dynamic behaviour of sporozoites in haemolymph and extracted salivary glands. Results A single fluorescent oocyst can be detected in live mosquitoes and P. berghei can infect A. albimanus. As in other mosquitoes, P. berghei sporozoites can float through the haemolymph and invade A. albimanus salivary glands and they are infectious in mice after subcutaneous injection. Conclusion Fluorescent Plasmodium parasites can be used to rapidly screen susceptible mosquitoes. These results open the way to develop a laboratory model in countries where importation of A. gambiae and A. stephensi is not allowed.

  1. Malaria, desnutrición y parasitosis intestinal en los niños colombianos: interrelaciones interrrelations between malaria, malnutrition and intestinal parasitism in colombian children

    Jaime Carmona Fonseca

    2004-09-01

    . lamblia (20%; 9 el estrés oxidativo se ha encontrado en los pacientes adultos de Turbo con malaria no complicada, ya sea vivax o falciparum, sin diferencia por especie. This paper reviews Colombian data as well as Grupo Malaria (Universidad de Antioquia findings on the relationship between malaria, malnutrition and immune response, observed in children (4-11 year old of Turbo, El Bagre and Zaragoza. These results and interpretations articulate with other studies about such relationships, including intestinal parasites. Emphasis is made on the association of malaria, intestinal parasites and malnutrition (chronic malnutrition, vitamin A deficit, that is explored through its articulation with the immune system. Clinical application (individual and epidemiological (collective recommendations are formulated towards vitamin A supplementation and use of wide spectrum antihelmintic therapy. In Turbo and El Bagre-Zaragoza: 1 malaria frequency during 1996-2000 registered annual parasite indexes of 39 (Turbo and 156 (El Bagre- Zaragoza; 2 chronic malnutrition risk (height/ age index was 63% in children aged 3-11; 3 anemia was observed in 26% of malaric children and in 17% of the non-malaric ones; 4 retinol was low (<0,3 µg/ml in 65% of children with malaria and in 35% of children without malaria; 5 apoprotein A-1 values were abnormally low in non-malaric children but they were lower in malaric children; 6 interleukin 10 levels were significantly higher in 96% of the malaric children (4-9 year old when compared to non-malaric children and to normal values; 7 total and specific anti-Plasmodium IgE and TNF-α were abnormally high in children of both municipalities; 8 among healthy teachers and nursing students aged 18-44, intestinal parasites were observed in 97%, while intestinal pathogenic parasites were detected in 42%. In 5 year old children of Turbo presence of pathogenic intestinal parasites was detected in 30-35%, with predominance of G. lamblia (20%; 9 oxidative stress was

  2. Estimating the numbers of malaria infections in blood samples using high-resolution genotyping data.

    Amanda Ross

    Full Text Available People living in endemic areas often habour several malaria infections at once. High-resolution genotyping can distinguish between infections by detecting the presence of different alleles at a polymorphic locus. However the number of infections may not be accurately counted since parasites from multiple infections may carry the same allele. We use simulation to determine the circumstances under which the number of observed genotypes are likely to be substantially less than the number of infections present and investigate the performance of two methods for estimating the numbers of infections from high-resolution genotyping data. The simulations suggest that the problem is not substantial in most datasets: the disparity between the mean numbers of infections and of observed genotypes was small when there was 20 or more alleles, 20 or more blood samples, a mean number of infections of 6 or less and where the frequency of the most common allele was no greater than 20%. The issue of multiple infections carrying the same allele is unlikely to be a major component of the errors in PCR-based genotyping. Simulations also showed that, with heterogeneity in allele frequencies, the observed frequencies are not a good approximation of the true allele frequencies. The first method that we proposed to estimate the numbers of infections assumes that they are a good approximation and hence did poorly in the presence of heterogeneity. In contrast, the second method by Li et al estimates both the numbers of infections and the true allele frequencies simultaneously and produced accurate estimates of the mean number of infections.

  3. Using remote sensing and modeling techniques to investigate the annual parasite incidence of malaria in Loreto, Peru

    Mousam, Aneela; Maggioni, Viviana; Delamater, Paul L.; Quispe, Antonio M.

    2017-10-01

    Between 2001 and 2010 significant progress was made towards reducing the number of malaria cases in Peru; however, the country saw an increase between 2011 and 2015. This work attempts to uncover the associations among various climatic and environmental variables and the annual malaria parasite incidence in the Peruvian region of Loreto. A Multilevel Mixed-effects Poisson Regression model is employed, focusing on the 2009-2013 period, when trends in malaria incidence shifted from decreasing to increasing. The results indicate that variations in elevation (β = 0.78; 95% confidence interval (CI), 0.75-0.81), soil moisture (β = 0.0021; 95% CI, 0.0019-0.0022), rainfall (β = 0.59; 95% CI, 0.56-0.61), and normalized difference vegetation index (β = 2.13; 95% CI, 1.83-2.43) is associated with higher annual parasite incidence, whereas an increase in temperature (β = -0.0043; 95% CI, - 0.0044- 0.0041) is associated with a lower annual parasite incidence. The results from this study are particularly useful for healthcare workers in Loreto and have the potential of being integrated within malaria elimination plans.

  4. Epilepsy and tropical parasitic infections in Sub-Saharan Africa: a ...

    Saharan Africa is associated with the high prevalence of parasitic infections affecting the central nervous system. Though epidemiological evidence suggests an association between parasitic infections and epilepsy, the biological causal ...

  5. Changes to cholesterol trafficking in macrophages by Leishmania parasites infection.

    Semini, Geo; Paape, Daniel; Paterou, Athina; Schroeder, Juliane; Barrios-Llerena, Martin; Aebischer, Toni

    2017-08-01

    Leishmania spp. are protozoan parasites that are transmitted by sandfly vectors during blood sucking to vertebrate hosts and cause a spectrum of diseases called leishmaniases. It has been demonstrated that host cholesterol plays an important role during Leishmania infection. Nevertheless, little is known about the intracellular distribution of this lipid early after internalization of the parasite. Here, pulse-chase experiments with radiolabeled cholesteryl esterified to fatty acids bound to low-density lipoproteins indicated that retention of this source of cholesterol is increased in parasite-containing subcellular fractions, while uptake is unaffected. This is correlated with a reduction or absence of detectable NPC1 (Niemann-Pick disease, type C1), a protein responsible for cholesterol efflux from endocytic compartments, in the Leishmania mexicana habitat and infected cells. Filipin staining revealed a halo around parasites within parasitophorous vacuoles (PV) likely representing free cholesterol accumulation. Labeling of host cell membranous cholesterol by fluorescent cholesterol species before infection revealed that this pool is also trafficked to the PV but becomes incorporated into the parasites' membranes and seems not to contribute to the halo detected by filipin. This cholesterol sequestration happened early after infection and was functionally significant as it correlated with the upregulation of mRNA-encoding proteins required for cholesterol biosynthesis. Thus, sequestration of cholesterol by Leishmania amastigotes early after infection provides a basis to understand perturbation of cholesterol-dependent processes in macrophages that were shown previously by others to be necessary for their proper function in innate and adaptive immune responses. © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  6. Antibody isotype analysis of malaria-nematode co-infection: problems and solutions associated with cross-reactivity

    Graham Andrea L

    2010-02-01

    Full Text Available Abstract Background Antibody isotype responses can be useful as indicators of immune bias during infection. In studies of parasite co-infection however, interpretation of immune bias is complicated by the occurrence of cross-reactive antibodies. To confidently attribute shifts in immune bias to the presence of a co-infecting parasite, we suggest practical approaches to account for antibody cross-reactivity. The potential for cross-reactive antibodies to influence disease outcome is also discussed. Results Utilising two murine models of malaria-helminth co-infection we analysed antibody responses of mice singly- or co-infected with Plasmodium chabaudi chabaudi and Nippostrongylus brasiliensis or Litomosoides sigmodontis. We observed cross-reactive antibody responses that recognised antigens from both pathogens irrespective of whether crude parasite antigen preparations or purified recombinant proteins were used in ELISA. These responses were not apparent in control mice. The relative strength of cross-reactive versus antigen-specific responses was determined by calculating antibody titre. In addition, we analysed antibody binding to periodate-treated antigens, to distinguish responses targeted to protein versus carbohydrate moieties. Periodate treatment affected both antigen-specific and cross-reactive responses. For example, malaria-induced cross-reactive IgG1 responses were found to target the carbohydrate component of the helminth antigen, as they were not detected following periodate treatment. Interestingly, periodate treatment of recombinant malaria antigen Merozoite Surface Protein-119 (MSP-119 resulted in increased detection of antigen-specific IgG2a responses in malaria-infected mice. This suggests that glycosylation may have been masking protein epitopes and that periodate-treated MSP-119 may more closely reflect the natural non-glycosylated antigen seen during infection. Conclusions In order to utilize antibody isotypes as a measure of

  7. Congenital malaria in China.

    Zhi-Yong Tao

    2014-03-01

    Full Text Available BACKGROUND: Congenital malaria, in which infants are directly infected with malaria parasites from their mother prior to or during birth, is a potentially life-threatening condition that occurs at relatively low rates in malaria-endemic regions. It is recognized as a serious problem in Plasmodium falciparum-endemic sub-Saharan Africa, where recent data suggests that it is more common than previously believed. In such regions where malaria transmission is high, neonates may be protected from disease caused by congenital malaria through the transfer of maternal antibodies against the parasite. However, in low P. vivax-endemic regions, immunity to vivax malaria is low; thus, there is the likelihood that congenital vivax malaria poses a more significant threat to newborn health. Malaria had previously been a major parasitic disease in China, and congenital malaria case reports in Chinese offer valuable information for understanding the risks posed by congenital malaria to neonatal health. As most of the literature documenting congenital malaria cases in China are written in Chinese and therefore are not easily accessible to the global malaria research community, we have undertaken an extensive review of the Chinese literature on this subject. METHODS/PRINCIPAL FINDINGS: Here, we reviewed congenital malaria cases from three major searchable Chinese journal databases, concentrating on data from 1915 through 2011. Following extensive screening, a total of 104 cases of congenital malaria were identified. These cases were distributed mainly in the eastern, central, and southern regions of China, as well as in the low-lying region of southwest China. The dominant species was P. vivax (92.50%, reflecting the malaria parasite species distribution in China. The leading clinical presentation was fever, and other clinical presentations were anaemia, jaundice, paleness, diarrhoea, vomiting, and general weakness. With the exception of two cases, all patients

  8. Autophagy-related Atg8 localizes to the apicoplast of the human malaria parasite Plasmodium falciparum.

    Kei Kitamura

    Full Text Available Autophagy is a membrane-mediated degradation process, which is governed by sequential functions of Atg proteins. Although Atg proteins are highly conserved in eukaryotes, protozoa possess only a partial set of Atg proteins. Nonetheless, almost all protozoa have the complete factors belonging to the Atg8 conjugation system, namely, Atg3, Atg4, Atg7, and Atg8. Here, we report the biochemical properties and subcellular localization of the Atg8 protein of the human malaria parasite Plasmodium falciparum (PfAtg8. PfAtg8 is expressed during intra-erythrocytic development and associates with membranes likely as a lipid-conjugated form. Fluorescence microscopy and immunoelectron microscopy show that PfAtg8 localizes to the apicoplast, a four membrane-bound non-photosynthetic plastid. Autophagosome-like structures are not observed in the erythrocytic stages. These data suggest that, although Plasmodium parasites have lost most Atg proteins during evolution, they use the Atg8 conjugation system for the unique organelle, the apicoplast.

  9. The malaria parasite RhopH protein complex interacts with erythrocyte calmyrin identified from a comprehensive erythrocyte protein library.

    Miura, Toyokazu; Takeo, Satoru; Ntege, Edward H; Otsuki, Hitoshi; Sawasaki, Tatsuya; Ishino, Tomoko; Takashima, Eizo; Tsuboi, Takafumi

    2018-06-02

    Malaria merozoite apical organelles; microneme and rhoptry secreted proteins play functional roles during and following invasion of host erythrocytes. Among numerous proteins, the rhoptries discharge high molecular weight proteins known as RhopH complex. Recent reports suggest that the RhopH complex is essential for growth and survival of the malaria parasite within erythrocytes. However, an in-depth understanding of the host-parasite molecular interactions is indispensable. Here we utilized a comprehensive mouse erythrocyte protein library consisting of 443 proteins produced by a wheat germ cell-free system, combined with AlphaScreen technology to identify mouse erythrocyte calmyrin as an interacting molecule of the rodent malaria parasite Plasmodium yoelii RhopH complex (PyRhopH). The PyRhopH interaction was dependent on the calmyrin N-terminus and divalent cation capacity. The finding unveils a recommendable and invaluable usefulness of our comprehensive mouse erythrocyte protein library together with the AlphaScreen technology in investigating a wide-range of host-parasite molecular interactions. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Pregnant women carrying female fetuses are at higher risk of placental malaria infection.

    Ishag Adam

    Full Text Available The pathophysiology of the placental malaria is not fully understood. If there is a fetal sex-specific susceptibility to malaria infection, this might add to the previous knowledge on the immunology, endocrinology and pathophysiology of placental malaria infections.This study was conducted to assess whether the sex of the fetus was associated with placental malaria infections.A cross-sectional study was performed including a secondary analysis of a cohort of women who were investigated for prevalence and risk factors (including fetal sex for placental malaria in eastern Sudan. Placental histology was used to diagnose placental malaria infections.Among 339 women enrolled, the mean (SD age was 25.8 (6.7 years and parity was 2.7 (2.2. Among the new born babies, 157 (46.3% were male and 182 (53.7% were female. Five (1.5%, 9 (2.7% and 103 (30.4% of the 339 placentas had active, active-chronic, past-chronic malaria infection on histopathology examination respectively, while 222 (65.5% of them showed no malaria infection. Logistic regression analyses showed no associations between maternal age or parity and placental malaria infections. Women who have blood group O (OR = 1.95, 95% CI = 1.19-3.10; P = 0.007 and women who had female new born were at higher risk for placental malaria infections (OR = 2.55, 95% CI = 1.57-4.13; P< 0.001.Fetal gender may be a novel risk factor for placental malaria. In this work the female placentas were at higher risk for malaria infections than the male placentas.

  11. Practical parasitology courses and infection with intestinal parasites in students.

    Fallahi, Sh; Rostami, A; Mohammadi, M; Ebrahimzadeh, F; Pournia, Y

    2016-01-01

    Students who are working in research or educational laboratories of parasitology, as well as health care workers providing care for patients, are at the risk of becoming infected with parasites through accidental exposure. The main purpose of this study was to identify potential positive cases of intestinal parasitic infections among students who took practical parasitology courses compared with students who did not take any practical parasitology courses in Lorestan University of Medical Sciences, Khorramabad, Iran, in 2013-2014. A total of 310 subjects from various majors were invited to voluntarily participate in the study. Various demographic data were collected using questionnaires. Three stool samples were collected from each individual on alternate days. Saline wet mounts (SWM), formalin-ether sedimentation test (FEST), Sheather floatation test (SHFT) and trichrome and modified Ziehl-Neelsen staining methods were used to diagnose the presence of intestinal parasites. The prevalence rate of intestinal parasites (IPs) among the students was 11.93%. There was a significant difference between majors in the infection with IPs (Pparasites in the educational course of practical parasitology could occur and must be taken into careful consideration. Copyright © 2015 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

  12. Unique physiology of host-parasite interactions in microsporidia infections.

    Williams, Bryony A P

    2009-11-01

    Microsporidia are intracellular parasites of all major animal lineages and have a described diversity of over 1200 species and an actual diversity that is estimated to be much higher. They are important pathogens of mammals, and are now one of the most common infections among immunocompromised humans. Although related to fungi, microsporidia are atypical in genomic biology, cell structure and infection mechanism. Host cell infection involves the rapid expulsion of a polar tube from a dormant spore to pierce the host cell membrane and allow the direct transfer of the spore contents into the host cell cytoplasm. This intimate relationship between parasite and host is unique. It allows the microsporidia to be highly exploitative of the host cell environment and cause such diverse effects as the induction of hypertrophied cells to harbour prolific spore development, host sex ratio distortion and host cell organelle and microtubule reorganization. Genome sequencing has revealed that microsporidia have achieved this high level of parasite sophistication with radically reduced proteomes and with many typical eukaryotic pathways pared-down to what appear to be minimal functional units. These traits make microsporidia intriguing model systems for understanding the extremes of reductive parasite evolution and host cell manipulation.

  13. Challenges in the management of intraocular parasitic infections

    Ashish Mitra

    2015-01-01

    Full Text Available Parasitic worms in eye is something which is not very uncommon these days. People who eat undercooked food and have pets at home are at more risk to have parasitic infections. Chemoparalysis has been reported in literature using either viscoelastics or preservative free lidocaine (intracamerally to paralyze the worms that help in retrieval, but still one can face tricky situations while managing such conditions. Importance lies in the management of such cases as it can be really challenging at times and no report exists in the literature which mentions the importance of topical lidocaine along with viscoelastics or preservative free lidocaine for retrieval of the worm.

  14. Effect of antenatal parasitic infections on anti-vaccine IgG levels in children: a prospective birth cohort study in Kenya.

    Indu Malhotra

    2015-01-01

    Full Text Available Parasitic infections are prevalent among pregnant women in sub-Saharan Africa. We investigated whether prenatal exposure to malaria and/or helminths affects the pattern of infant immune responses to standard vaccinations against Haemophilus influenzae (Hib, diphtheria (DT, hepatitis B (Hep B and tetanus toxoid (TT.450 Kenyan women were tested for malaria, schistosomiasis, lymphatic filariasis (LF, and intestinal helminths during pregnancy. After three standard vaccinations at 6, 10 and 14 weeks, their newborns were followed biannually to age 36 months and tested for absolute levels of IgG against Hib, DT, Hep B, and TT at each time point. Newborns' cord blood (CB lymphocyte responses to malaria blood-stage antigens, soluble Schistosoma haematobium worm antigen (SWAP, and filaria antigen (BMA were also assessed. Three immunophenotype categories were compared: i tolerant (those having Plasmodium-, Schistosoma-, or Wuchereria-infected mothers but lacking respective Th1/Th2-type recall responses at birth to malaria antigens, SWAP, or BMA; ii sensitized (those with infected/uninfected mothers and detectable Th1/Th2-type CB recall response to respective parasite antigen; or iii unexposed (no evidence of maternal infection or CB recall response. Overall, 78.9% of mothers were infected with LF (44.7%, schistosomiasis (32.4%, malaria (27.6% or hookworm (33.8%. Antenatal maternal malaria, LF, and hookworm were independently associated with significantly lower Hib-specific IgG. Presence of multiple maternal infections was associated with lower infant IgG levels against Hib and DT antigens post-vaccination. Post-vaccination IgG levels were also significantly associated with immunophenotype: malaria-tolerized infants had reduced response to DT, whereas filaria-tolerized infants showed reduced response to Hib.There is an impaired ability to develop IgG antibody responses to key protective antigens of Hib and diphtheria in infants of mothers infected with

  15. The past, present and future use of epidemiological intelligence to plan malaria vector control and parasite prevention in Uganda.

    Talisuna, Ambrose O; Noor, Abdisalan M; Okui, Albert P; Snow, Robert W

    2015-04-15

    An important prelude to developing strategies to control infectious diseases is a detailed epidemiological evidence platform to target cost-effective interventions and define resource needs. A review of published and un-published reports of malaria vector control and parasite prevention in Uganda was conducted for the period 1900-2013. The objective was to provide a perspective as to how epidemiological intelligence was used to design malaria control before and during the global malaria eradication programme (GMEP) and to contrast this with the evidence generated in support of the Roll Back Malaria (RBM) initiative from 1998 to date. During the GMEP era, comprehensive investigations were undertaken on the effectiveness of vector and parasite control such as indoor residual house-spraying (IRS) and mass drug administration (MDA) at different sites in Uganda. Nationwide malariometric surveys were undertaken between 1964 and 1967 to provide a profile of risk, epidemiology and seasonality leading to an evidence-based national cartography of risk to characterize the diversity of malaria transmission in Uganda. At the launch of the RBM initiative in the late 1990s, an equivalent level of evidence was lacking. There was no contemporary national evidence-base for the likely impact of insecticide-treated nets (ITN), no new malariometric data, no new national cartography of malaria risk or any evidence of tailored intervention delivery based on variations in the ecology of malaria risk in Uganda. Despite millions of dollars of overseas development assistance over the last ten years in ITN, and more recently the resurrection of the use of IRS, the epidemiological impact of vector control remains uncertain due to an absence of nationwide basic parasite and vector-based field studies. Readily available epidemiological data should become the future business model to maximize malaria funding from 2015. Over the next five to ten years, accountability, impact analysis, financial

  16. Falciparum malaria infection with invasive pulmonary aspergillosis in immunocompetent host – case report

    Andriyani, Y.

    2018-03-01

    Invasive pulmonary aspergillosis is an extraordinary rare in the immunocompetent host. Falciparum malaria contributes to high morbidity and mortality of malaria infection cases in the world. The impairments of both humoral and cellular immunity could be the reason of invasive pulmonary aspergillosis in falciparum malaria infection. Forty-nine years old patient came with fever, jaundice, pain in the right abdomen, after visiting a remote area in Africa about one month before admission. Blood films and rapid test were positive for Plasmodium falciparum. After malaria therapy in five days, consciousness was altered into somnolence and intubated with respiratory deterioration. Invasive pulmonary aspergillosis after falciparum malaria infection is life-threatening. There should be awareness of physicians of invasive pulmonary aspergillosis in falciparum malaria infection.

  17. Mathematical modeling of malaria infection with innate and adaptive immunity in individuals and agent-based communities.

    Gurarie, David; Karl, Stephan; Zimmerman, Peter A; King, Charles H; St Pierre, Timothy G; Davis, Timothy M E

    2012-01-01

    Agent-based modeling of Plasmodium falciparum infection offers an attractive alternative to the conventional Ross-Macdonald methodology, as it allows simulation of heterogeneous communities subjected to realistic transmission (inoculation patterns). We developed a new, agent based model that accounts for the essential in-host processes: parasite replication and its regulation by innate and adaptive immunity. The model also incorporates a simplified version of antigenic variation by Plasmodium falciparum. We calibrated the model using data from malaria-therapy (MT) studies, and developed a novel calibration procedure that accounts for a deterministic and a pseudo-random component in the observed parasite density patterns. Using the parasite density patterns of 122 MT patients, we generated a large number of calibrated parameters. The resulting data set served as a basis for constructing and simulating heterogeneous agent-based (AB) communities of MT-like hosts. We conducted several numerical experiments subjecting AB communities to realistic inoculation patterns reported from previous field studies, and compared the model output to the observed malaria prevalence in the field. There was overall consistency, supporting the potential of this agent-based methodology to represent transmission in realistic communities. Our approach represents a novel, convenient and versatile method to model Plasmodium falciparum infection.

  18. Mathematical modeling of malaria infection with innate and adaptive immunity in individuals and agent-based communities.

    David Gurarie

    Full Text Available BACKGROUND: Agent-based modeling of Plasmodium falciparum infection offers an attractive alternative to the conventional Ross-Macdonald methodology, as it allows simulation of heterogeneous communities subjected to realistic transmission (inoculation patterns. METHODOLOGY/PRINCIPAL FINDINGS: We developed a new, agent based model that accounts for the essential in-host processes: parasite replication and its regulation by innate and adaptive immunity. The model also incorporates a simplified version of antigenic variation by Plasmodium falciparum. We calibrated the model using data from malaria-therapy (MT studies, and developed a novel calibration procedure that accounts for a deterministic and a pseudo-random component in the observed parasite density patterns. Using the parasite density patterns of 122 MT patients, we generated a large number of calibrated parameters. The resulting data set served as a basis for constructing and simulating heterogeneous agent-based (AB communities of MT-like hosts. We conducted several numerical experiments subjecting AB communities to realistic inoculation patterns reported from previous field studies, and compared the model output to the observed malaria prevalence in the field. There was overall consistency, supporting the potential of this agent-based methodology to represent transmission in realistic communities. CONCLUSIONS/SIGNIFICANCE: Our approach represents a novel, convenient and versatile method to model Plasmodium falciparum infection.

  19. Structural and functional insights into the malaria parasite moving junction complex.

    Brigitte Vulliez-Le Normand

    Full Text Available Members of the phylum Apicomplexa, which include the malaria parasite Plasmodium, share many features in their invasion mechanism in spite of their diverse host cell specificities and life cycle characteristics. The formation of a moving junction (MJ between the membranes of the invading apicomplexan parasite and the host cell is common to these intracellular pathogens. The MJ contains two key parasite components: the surface protein Apical Membrane Antigen 1 (AMA1 and its receptor, the Rhoptry Neck Protein (RON complex, which is targeted to the host cell membrane during invasion. In particular, RON2, a transmembrane component of the RON complex, interacts directly with AMA1. Here, we report the crystal structure of AMA1 from Plasmodium falciparum in complex with a peptide derived from the extracellular region of PfRON2, highlighting clear specificities of the P. falciparum RON2-AMA1 interaction. The receptor-binding site of PfAMA1 comprises the hydrophobic groove and a region that becomes exposed by displacement of the flexible Domain II loop. Mutations of key contact residues of PfRON2 and PfAMA1 abrogate binding between the recombinant proteins. Although PfRON2 contacts some polymorphic residues, binding studies with PfAMA1 from different strains show that these have little effect on affinity. Moreover, we demonstrate that the PfRON2 peptide inhibits erythrocyte invasion by P. falciparum merozoites and that this strong inhibitory potency is not affected by AMA1 polymorphisms. In parallel, we have determined the crystal structure of PfAMA1 in complex with the invasion-inhibitory peptide R1 derived by phage display, revealing an unexpected structural mimicry of the PfRON2 peptide. These results identify the key residues governing the interactions between AMA1 and RON2 in P. falciparum and suggest novel approaches to antimalarial therapeutics.

  20. Population genomic scan for candidate signatures of balancing selection to guide antigen characterization in malaria parasites.

    Amambua-Ngwa, Alfred; Tetteh, Kevin K A; Manske, Magnus; Gomez-Escobar, Natalia; Stewart, Lindsay B; Deerhake, M Elizabeth; Cheeseman, Ian H; Newbold, Christopher I; Holder, Anthony A; Knuepfer, Ellen; Janha, Omar; Jallow, Muminatou; Campino, Susana; Macinnis, Bronwyn; Kwiatkowski, Dominic P; Conway, David J

    2012-01-01

    Acquired immunity in vertebrates maintains polymorphisms in endemic pathogens, leading to identifiable signatures of balancing selection. To comprehensively survey for genes under such selection in the human malaria parasite Plasmodium falciparum, we generated paired-end short-read sequences of parasites in clinical isolates from an endemic Gambian population, which were mapped to the 3D7 strain reference genome to yield high-quality genome-wide coding sequence data for 65 isolates. A minority of genes did not map reliably, including the hypervariable var, rifin, and stevor families, but 5,056 genes (90.9% of all in the genome) had >70% sequence coverage with minimum read depth of 5 for at least 50 isolates, of which 2,853 genes contained 3 or more single nucleotide polymorphisms (SNPs) for analysis of polymorphic site frequency spectra. Against an overall background of negatively skewed frequencies, as expected from historical population expansion combined with purifying selection, the outlying minority of genes with signatures indicating exceptionally intermediate frequencies were identified. Comparing genes with different stage-specificity, such signatures were most common in those with peak expression at the merozoite stage that invades erythrocytes. Members of clag, PfMC-2TM, surfin, and msp3-like gene families were highly represented, the strongest signature being in the msp3-like gene PF10_0355. Analysis of msp3-like transcripts in 45 clinical and 11 laboratory adapted isolates grown to merozoite-containing schizont stages revealed surprisingly low expression of PF10_0355. In diverse clonal parasite lines the protein product was expressed in a minority of mature schizonts (<1% in most lines and ∼10% in clone HB3), and eight sub-clones of HB3 cultured separately had an intermediate spectrum of positive frequencies (0.9 to 7.5%), indicating phase variable expression of this polymorphic antigen. This and other identified targets of balancing selection are now

  1. Population genomic scan for candidate signatures of balancing selection to guide antigen characterization in malaria parasites.

    Alfred Amambua-Ngwa

    Full Text Available Acquired immunity in vertebrates maintains polymorphisms in endemic pathogens, leading to identifiable signatures of balancing selection. To comprehensively survey for genes under such selection in the human malaria parasite Plasmodium falciparum, we generated paired-end short-read sequences of parasites in clinical isolates from an endemic Gambian population, which were mapped to the 3D7 strain reference genome to yield high-quality genome-wide coding sequence data for 65 isolates. A minority of genes did not map reliably, including the hypervariable var, rifin, and stevor families, but 5,056 genes (90.9% of all in the genome had >70% sequence coverage with minimum read depth of 5 for at least 50 isolates, of which 2,853 genes contained 3 or more single nucleotide polymorphisms (SNPs for analysis of polymorphic site frequency spectra. Against an overall background of negatively skewed frequencies, as expected from historical population expansion combined with purifying selection, the outlying minority of genes with signatures indicating exceptionally intermediate frequencies were identified. Comparing genes with different stage-specificity, such signatures were most common in those with peak expression at the merozoite stage that invades erythrocytes. Members of clag, PfMC-2TM, surfin, and msp3-like gene families were highly represented, the strongest signature being in the msp3-like gene PF10_0355. Analysis of msp3-like transcripts in 45 clinical and 11 laboratory adapted isolates grown to merozoite-containing schizont stages revealed surprisingly low expression of PF10_0355. In diverse clonal parasite lines the protein product was expressed in a minority of mature schizonts (<1% in most lines and ∼10% in clone HB3, and eight sub-clones of HB3 cultured separately had an intermediate spectrum of positive frequencies (0.9 to 7.5%, indicating phase variable expression of this polymorphic antigen. This and other identified targets of balancing

  2. Nuclear techniques in the control of parasitic infections

    Mulligan, W.

    1976-01-01

    The development of radiation-attenuated vaccines against economically important parasitic diseases of farm animals has met with mixed success. Examples are presented ranging from the highly effective and much used commercial vaccine against cattle lungworm to the almost completely unsuccessful attempts to immunize sheep against liver fluke. The results presented emphasize that this approach is likely to be successful only if there is evidence of a strong degree of acquired immunity to the natural infection. The extension of immunological control to those systems where the parasite provokes only a modest resistance by the host will probably depend on a much greater understanding of the mechanism of the immune response. Such fundamental studies are likely to rely heavily on nuclear techniques, e.g. in the labelling of antigens, antibodies and parasites with radioactive isotopes. (author)

  3. Identification of a Golgi apparatus protein complex important for the asexual erythrocytic cycle of the malaria parasite Plasmodium falciparum.

    Hallée, Stéphanie; Thériault, Catherine; Gagnon, Dominic; Kehrer, Jessica; Frischknecht, Friedrich; Mair, Gunnar R; Richard, Dave

    2018-03-26

    Compared with other eukaryotic cell types, malaria parasites appear to possess a more rudimentary Golgi apparatus being composed of dispersed, unstacked cis and trans-cisternae. Despite playing a central role in the secretory pathway of the parasite, few Plasmodium Golgi resident proteins have been characterised. We had previously identified a new Golgi resident protein of unknown function, which we had named Golgi Protein 1, and now show that it forms a complex with a previously uncharacterised transmembrane protein (Golgi Protein 2, GP2). The Golgi Protein complex localises to the cis-Golgi throughout the erythrocytic cycle and potentially also during the mosquito stages. Analysis of parasite strains where GP1 expression is conditionally repressed and/or the GP2 gene is inactivated reveals that though the Golgi protein complex is not essential at any stage of the parasite life cycle, it is important for optimal asexual development in the blood stages. © 2018 John Wiley & Sons Ltd.

  4. Manual blood exchange transfusion does not significantly contribute to parasite clearance in artesunate-treated individuals with imported severe Plasmodium falciparum malaria

    Kreeftmeijer-Vegter, Annemarie R.; Melo, Mariana de Mendonça; de Vries, Peter J.; Koelewijn, Rob; van Hellemond, Jaap J.; van Genderen, Perry J. J.

    2013-01-01

    Exchange transfusion (ET) has remained a controversial adjunct therapy for the treatment of severe malaria. In order to assess the relative contribution of ET to parasite clearance in severe malaria, all patients receiving ET as an adjunct treatment to parenteral quinine or to artesunate were

  5. Manual blood exchange transfusion does not significantly contribute to parasite clearance in artesunate-treated individuals with imported severe Plasmodium falciparum malaria

    A.R. Kreeftmeijer-Vegter (Annemarie); M.M. de Melo (Mariana ); P.J. de Vries (Peter); R. Koelewijn (Rob); J.J. van Hellemond (Jaap); P.J.J. van Genderen (Perry)

    2013-01-01

    textabstractBackground: Exchange transfusion (ET) has remained a controversial adjunct therapy for the treatment of severe malaria. In order to assess the relative contribution of ET to parasite clearance in severe malaria, all patients receiving ET as an adjunct treatment to parenteral quinine or

  6. Tracking transparent monogenean parasites on fish from infection to maturity

    Alejandro Trujillo-González

    2015-12-01

    Full Text Available The infection dynamics and distribution of the ectoparasitic fish monogenean Neobenedenia sp. (Monogenea: Capsalidae throughout its development was examined on barramundi, Lates calcarifer (Bloch (Latidae, by labelling transparent, ciliated larvae (oncomiracidia with a fluorescent dye. Replicate fish were each exposed to approximately 50 fluorescent oncomiracidia and then examined for parasites using an epifluorescence stereomicroscope at 10 time intervals post-exposure (15, 30, 60, 120 min, 24, 48 h, four, eight, 12, and 16 days. Fluorescent labelling revealed that parasites attached underneath and on the surface of the scales of host fish. Parasite infection success was 20% within 15 min, and peaked at 93% two days post-exposure, before gradually declining between four and sixteen days. Differences in parasite distribution on L. calcarifer over time provided strong evidence that Neobenedenia sp. larvae settled opportunistically and then migrated to specific microhabitats. Parasites initially attached (<24 h in greater mean numbers on the body surface (13 ± 1.5 compared to the fins (4 ± 0.42 and head region (2 ± 0.41. Once larvae recruitment had ceased (48 h, there were significantly higher mean post-larvae counts on the head (5 ± 3.4 and fins (12 ± 3 compared to previous time intervals. Neobenedenia sp. aggregated on the eyes, fins, and dorsal and ventral extremities on the main body. As parasites neared sexual maturity, there was a marked aggregation on the fins (22 ± 2.35 compared to the head (4 ± 0.97 and body (9 ± 1.33, indicating that Neobenedenia sp. may form mating aggregations.

  7. Malaria and Hepatitis B co-infection in patients with febrile illnesses ...

    Malaria and Hepatitis B Virus (HBV) infections are co-endemic throughout much of the tropical and sub-Saharan Africa and both present major threat to public health. A study on the prevalence of HBV and Malaria co-infection was carried out on 200 patients presenting with fever at the General Outpatient Department ...

  8. Molecular Evidence of Drug Resistance in Asymptomatic Malaria Infections, Myanmar, 2015.

    Nyunt, Myat Htut; Shein, Thinzar; Zaw, Ni Ni; Han, Soe Soe; Muh, Fauzi; Lee, Seong-Kyun; Han, Jin-Hee; Thant, Kyaw Zin; Han, Eun-Taek; Kyaw, Myat Phone

    2017-03-01

    Artemisinin resistance containment in Myanmar was initiated in 2011 after artemisinin-resistant Plasmodium falciparum malaria was reported. Molecular evidence suggests that asymptomatic malaria infections harboring drug resistance genes are present among residents of the Myanmar artemisinin resistance containment zone. This evidence supports efforts to eliminate these hidden infections.

  9. Epidemiological Study of the Association Between Malaria and Helminth Infections in Nigeria

    Efunshile, Akinwale Michael; Olawale, Temitope; Stensvold, Christen Rune

    2015-01-01

    The relationship between intestinal helminth infection and susceptibility to malaria remains unclear. We studied the relationship between these infections. Seven schools in Ilero, Nigeria referred all pupils with febrile illness to our study center for free malaria treatment during a 3-month stud...

  10. Controlled Human Malaria Infection of Tanzanians by Intradermal Injection of Aseptic, Purified, Cryopreserved Plasmodium falciparum Sporozoites

    Shekalaghe, S.; Rutaihwa, M.; Billingsley, P.F.; Chemba, M.; Daubenberger, C.A.; James, E.R.; Mpina, M.; Juma, O. Ali; Schindler, T.; Huber, E.; Gunasekera, A.; Manoj, A.; Simon, B.; Saverino, E.; Church, L.W.; Hermsen, C.C.; Sauerwein, R.W.; Plowe, C.; Venkatesan, M.; Sasi, P.; Lweno, O.; Mutani, P.; Hamad, A.; Mohammed, A.; Urassa, A.; Mzee, T.; Padilla, D.; Ruben, A.; Sim, B.K.; Tanner, M.; Abdulla, S.; Hoffman, S.L.

    2014-01-01

    Controlled human malaria infection (CHMI) by mosquito bite has been used to assess anti-malaria interventions in > 1,500 volunteers since development of methods for infecting mosquitoes by feeding on Plasmodium falciparum (Pf) gametocyte cultures. Such CHMIs have never been used in Africa. Aseptic,

  11. Nutritional status and malaria infection in primary school-aged children

    Washli Zakiah

    2015-07-01

    Conclusion There are significantly more children with mild-moderate malnutrition in the uninfected group than in the malaria-infected group, furthermore, of those with mild-moderate malnutrition, there are significantly more stunted and stunted-wasted children who were uninfected than malaria-infected.

  12. Effect of HIV-1 infection on malaria treatment outcome in Ugandan ...

    Background: Malaria and HIV-1 infection cause significant morbidity and mortality in sub-Saharan Africa. HIV-1 increases risk for malaria with the risk increasing as immunity declines.The effect of HIV-1 infection on antimalarial treatment outcome is still inconclusive. Objective: To compare antimalarial treatment outcome ...

  13. Plasmodium cysteine repeat modular proteins 1-4: complex proteins with roles throughout the malaria parasite life cycle.

    Thompson, Joanne; Fernandez-Reyes, Delmiro; Sharling, Lisa; Moore, Sally G; Eling, Wijnand M; Kyes, Sue A; Newbold, Christopher I; Kafatos, Fotis C; Janse, Chris J; Waters, Andrew P

    2007-06-01

    The Cysteine Repeat Modular Proteins (PCRMP1-4) of Plasmodium, are encoded by a small gene family that is conserved in malaria and other Apicomplexan parasites. They are very large, predicted surface proteins with multipass transmembrane domains containing motifs that are conserved within families of cysteine-rich, predicted surface proteins in a range of unicellular eukaryotes, and a unique combination of protein-binding motifs, including a >100 kDa cysteine-rich modular region, an epidermal growth factor-like domain and a Kringle domain. PCRMP1 and 2 are expressed in life cycle stages in both the mosquito and vertebrate. They colocalize with PfEMP1 (P. falciparum Erythrocyte Membrane Antigen-1) during its export from P. falciparum blood-stage parasites and are exposed on the surface of haemolymph- and salivary gland-sporozoites in the mosquito, consistent with a role in host tissue targeting and invasion. Gene disruption of pcrmp1 and 2 in the rodent malaria model, P. berghei, demonstrated that both are essential for transmission of the parasite from the mosquito to the mouse and has established their discrete and important roles in sporozoite targeting to the mosquito salivary gland. The unprecedented expression pattern and structural features of the PCRMPs thus suggest a variety of roles mediating host-parasite interactions throughout the parasite life cycle.

  14. Malaria Parasite Infection and Chloroquine-Induced Pruritus: The ...

    induced body scratching, whereas, the histaminergic system was implicated in CQ-induced itching. Keywords: Rats, parasitaemia, chloroquine, opioids, antihistamine, naltrexone. West African Journal of Pharmacology and Drug Research Vol.

  15. T-cell responses in malaria

    Hviid, L; Jakobsen, P H; Abu-Zeid, Y A

    1992-01-01

    Malaria is caused by infection with protozoan parasites of the genus Plasmodium. It remains one of the most severe health problems in tropical regions of the world, and the rapid spread of resistance to drugs and insecticides has stimulated intensive research aimed at the development of a malaria...... vaccine. Despite this, no efficient operative vaccine is currently available. A large amount of information on T-cell responses to malaria antigens has been accumulated, concerning antigens derived from all stages of the parasite life cycle. The present review summarizes some of that information......, and discusses factors affecting the responses of T cells to malaria antigens....

  16. Parasitic helminth infections in native sheep (Mehraban in Hamedan, Iran

    Jamal Gharekhani

    2015-06-01

    Full Text Available Sheep play an important role in national economy and social economy in rural areas in Iran. The main goal of this study was to investigate the fauna and frequency of parasitic helminth infections prevalent in native sheep in Hamedan, western Iran. From April 2010 to March 2011, the gastrointestinal and respiratory tracts of 100-sheep were examined using conventional parasitological methods. The overall infection rate was found as 69%. No infection was found in esophagus and rumens. Parabronema skerjabini (22% and Ostertagia circumcincta (1% were recorded as the maximum and minimum cases for the presence of nematode, respectively. On the other hand, the most dominant of trematode and cestode were Fasciola hepatica (13% and Monezia expansa (13%, respectively. The highest infection rate was reported in summer (84%. The prevalence of helminth infection was varied among gender, seasons and age groups. In conclusion, this is the first report of parasitic helminth infections in sheep in Hamedan province in western Iran. Our results provide baseline information for the future studies.

  17. Global histone analysis by mass spectrometry reveals a high content of acetylated lysine residues in the malaria parasite Plasmodium falciparum

    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....

  18. Septic Shock due to Cytomegalovirus Infection in Acute Respiratory Distress Syndrome after Falciparum Malaria.

    Harbarth; Meyer; Grau; Loutan; Ricou

    1997-09-01

    Incidence of falciparum malaria in developed countries has increased in recent years due to tourism to tropical countries and immigration from Asia and Africa. In Switzerland, about 250 cases of malaria were reported in 1994 to the Federal Office of Health, including three cases with fatal outcome.1 The most commonly described complications of plasmodia infection are cerebral malaria, acute renal failure, and severe anemia with disseminated intravascular coagulation. However, pulmonary involvement occurs in 3 to 10% of cases and represents the most serious complication of this infection, with a lethality of 70%.2,3 Furthermore, a pronounced general immunosuppression has been reported in malaria patients, which may predispose them to opportunistic infections.4 We report a case of Plasmodium falciparum infection complicated by severe acute respiratory distress syndrome (ARDS) with development of systemic cytomegalovirus (CMV) infection leading to death. This evolution implies a severe immune deficiency associated with malaria, as previously suggested in the literature.

  19. Molecular appraisal of intestinal parasitic infection in transplant recipients

    Pooja Yadav

    2016-01-01

    Full Text Available Background & objectives: Diarrhoea is the main clinical manifestation caused by intestinal parasitic infections in patients, with special reference to transplant recipients who require careful consideration to reduce morbidity and mortality. Further, molecular characterization of some important parasites is necessary to delineate the different modes of transmission to consider appropriate management strategies. We undertook this study to investigate the intestinal parasitic infections in transplant recipients with or without diarrhoea, and the genotypes of the isolated parasites were also determined. Methods: Stool samples from 38 transplant recipients comprising 29 post-renal, two liver and seven bone marrow transplant (BMT recipients presenting with diarrhoea and 50 transplant recipients (42 post-renal transplant, eight BMT without diarrhoea were examined for the presence of intestinal parasites by light microscopy using wet mount, modified Ziehl-Neelsen staining for intestinal coccidia and modified trichrome staining for microsporidia. Genotypes of Cryptosporidium species were determined by multilocus genotyping using small subunit ribosomal (SSUrRNA, Cryptosporidium oocyst wall protein (COWP and dihydrofolate reductase (DHFR as the target genes. Assemblage study for Giardia lamblia was performed using triose phosphate isomerase (TPI as the target gene. Samples were also screened for bacterial, fungal and viral pathogens. Results: The parasites that were detected included Cryptosporidium species (21%, 8/38, Cystoisospora (Isospora belli (8%, 3, Cyclospora cayetanensis (5%, 2, G. lamblia (11%, 4, Hymenolepis nana (11%, 4, Strongyloides stercoralis (3%, 1 and Blastocystis hominis (3%, 1. Multilocus genotyping of Cryptosporidium species at SSUrRNA, COWP and DHFR loci could detect four isolates of C. hominis; two of C. parvum, one of mixed genotype and one could not be genotyped. All the C. hominis isolates were detected in adult post

  20. Positive Selection of Plasmodium falciparum Parasites With Multiple var2csa-Type PfEMP1 Genes During the Course of Infection in Pregnant Women

    Salanti, Ali; Lavstsen, Thomas; Nielsen, Morten A.; Theander, Thor G.; Leke, Rose G. F.; Lo, Yeung Y.; Bobbili, Naveen; Arnot, David E.; Taylor, Diane W.

    2011-01-01

    Placental malaria infections are caused by Plasmodium falciparum–infected red blood cells sequestering in the placenta by binding to chondroitin sulfate A, mediated by VAR2CSA, a variant of the PfEMP1 family of adhesion antigens. Recent studies have shown that many P. falciparum genomes have multiple genes coding for different VAR2CSA proteins, and parasites with >1 var2csa gene appear to be more common in pregnant women with placental malaria than in nonpregnant individuals. We present evidence that, in pregnant women, parasites containing multiple var2csa-type genes possess a selective advantage over parasites with a single var2csa gene. Accumulation of parasites with multiple copies of the var2csa gene during the course of pregnancy was also correlated with the development of antibodies involved in blocking VAR2CSA adhesion. The data suggest that multiplicity of var2csa-type genes enables P. falciparum parasites to persist for a longer period of time during placental infections, probably because of their greater capacity for antigenic variation and evasion of variant-specific immune responses. PMID:21592998

  1. Intestinal Parasitic Infections among Pregnant Women in Venezuela

    2006-01-01

    Full Text Available Introduction. Intestinal parasitic infections, especially due to helminths, increase anemia in pregnant women. The results of this are low pregnancy weight gain and IUGR, followed by LBW, with its associated greater risks of infection and higher perinatal mortality rates. For these reasons, in the setting of no large previous studies in Venezuela about this problem, a national multicentric study was conducted. Methods. Pregnant women from nine states were studied, a prenatal evaluation with a coproparasitological study. Univariated and multivariated analyses were made to determine risk factors for intestinal parasitosis and related anemia. Results. During 19 months, 1038 pregnant women were included and evaluated. Intestinal parasitosis was evidenced in 73.9%: A lumbricoides 57.0%, T trichiura 36.0%, G lamblia 14.1%, E hystolitica 12.0%, N americanus 8.1%, E vermicularis 6.3%, S stercoralis 3.3%. Relative risk for anemia in those women with intestinal parasitosis was 2.56 ( P<.01 . Discussion. Intestinal parasitoses could be associated with conditions for development of anemia at pregnancy. These features reflect the need of routine coproparasitological study among pregnant women in rural and endemic zones for intestinal parasites. Further therapeutic and prophylactic protocols are needed. Additional research on pregnant intestinal parasitic infection impact on newborn health is also considered.

  2. Intestinal Parasitic Infections among Pregnant Women in Venezuela

    Rodríguez-Morales, Alfonso J.; Barbella, Rosa A.; Case, Cynthia; Arria, Melissa; Ravelo, Marisela; Perez, Henry; Urdaneta, Oscar; Gervasio, Gloria; Rubio, Nestor; Maldonado, Andrea; Aguilera, Ymora; Viloria, Anna; Blanco, Juan J.; Colina, Magdary; Hernández, Elizabeth; Araujo, Elianet; Cabaniel, Gilberto; Benitez, Jesús; Rifakis, Pedro

    2006-01-01

    Introduction. Intestinal parasitic infections, especially due to helminths, increase anemia in pregnant women. The results of this are low pregnancy weight gain and IUGR, followed by LBW, with its associated greater risks of infection and higher perinatal mortality rates. For these reasons, in the setting of no large previous studies in Venezuela about this problem, a national multicentric study was conducted. Methods. Pregnant women from nine states were studied, a prenatal evaluation with a coproparasitological study. Univariated and multivariated analyses were made to determine risk factors for intestinal parasitosis and related anemia. Results. During 19 months, 1038 pregnant women were included and evaluated. Intestinal parasitosis was evidenced in 73.9%: A lumbricoides 57.0%, T trichiura 36.0%, G lamblia 14.1%, E hystolitica 12.0%, N americanus 8.1%, E vermicularis 6.3%, S stercoralis 3.3%. Relative risk for anemia in those women with intestinal parasitosis was 2.56 (P Intestinal parasitoses could be associated with conditions for development of anemia at pregnancy. These features reflect the need of routine coproparasitological study among pregnant women in rural and endemic zones for intestinal parasites. Further therapeutic and prophylactic protocols are needed. Additional research on pregnant intestinal parasitic infection impact on newborn health is also considered. PMID:17093349

  3. The treatment of Plasmodium falciparum-infected erythrocytes with chloroquine leads to accumulation of ferriprotoporphyrin IX bound to particular parasite proteins and to the inhibition of the parasite's 6-phosphogluconate dehydrogenase

    Famin O.

    2003-03-01

    Full Text Available Ferriprotoporphyrin IX (FPIX is a potentially toxic product of hemoglobin digestion by intra-erythrocytic malaria parasites. It is detoxified by biomineralization or through degradation by glutathione. Both processes are inhibited by the antimalarial drug chloroquine, leading to the accumulation of FPIX in the membranes of the infected cell and their consequent permeabilization. It is shown here that treatment of Plasmodium falciparum-infected erythrocytes with chloroquine also leads to the binding of FPIX to a subset of parasite proteins. Parasite enzymes such as aldolase, pyrimidine nucleoside monophosphate kinase and pyrimidine 5'- nucleotidase were inhibited by FPIX in vitro, but only the activity of 6-phosphogluconate dehydrogenase was reduced significantly in cells after drug treatment. Additional proteins were extracted from parasite cytosol by their ability to bind FPIX. Sequencing of these proteins identified heat shock proteins 90 and 70, enolase, elongation factor 1-α, phoshoglycerate kinase, glyceraldehyde 3- phosphate dehydrogenase, L-lactate dehydrogenase and gametocytogenesis onset-specific protein. The possible involvement of these proteins in the antimalarial mode of action of chloroquine is discussed. It is concluded that drug-induced binding of FPIX to parasite glycolytic enzymes could underlie the demonstrable inhibition of glycolysis by chloroquine. The inhibition of 6- phosphogluconate dehydrogenase could explain the reduction of the activity of the hexose monophosphate shunt by the drug. Inhibition of both processes is deleterious to parasite survival. Binding of FPIX to other proteins is probably inconsequential to the rapid killing of the parasite by chloroquine.

  4. A cyclic GMP signalling module that regulates gliding motility in a malaria parasite.

    Robert W Moon

    2009-09-01

    Full Text Available The ookinete is a motile stage in the malaria life cycle which forms in the mosquito blood meal from the zygote. Ookinetes use an acto-myosin motor to glide towards and penetrate the midgut wall to establish infection in the vector. The regulation of gliding motility is poorly understood. Through genetic interaction studies we here describe a signalling module that identifies guanosine 3', 5'-cyclic monophosphate (cGMP as an important second messenger regulating ookinete differentiation and motility. In ookinetes lacking the cyclic nucleotide degrading phosphodiesterase delta (PDEdelta, unregulated signalling through cGMP results in rounding up of the normally banana-shaped cells. This phenotype is suppressed in a double mutant additionally lacking guanylyl cyclase beta (GCbeta, showing that in ookinetes GCbeta is an important source for cGMP, and that PDEdelta is the relevant cGMP degrading enzyme. Inhibition of the cGMP-dependent protein kinase, PKG, blocks gliding, whereas enhanced signalling through cGMP restores normal gliding speed in a mutant lacking calcium dependent protein kinase 3, suggesting at least a partial overlap between calcium and cGMP dependent pathways. These data demonstrate an important function for signalling through cGMP, and most likely PKG, in dynamically regulating ookinete gliding during the transmission of malaria to the mosquito.

  5. The double edge to parasite escape: invasive host is less infected but more infectable.

    Keogh, Carolyn L; Miura, Osamu; Nishimura, Tomohiro; Byers, James E

    2017-09-01

    Nonnative species that escape their native-range parasites may benefit not only from reduced infection pathology, but also from relaxed selection on costly immune defenses, promoting reallocation of resources toward growth or reproduction. However, benefits accruing from a reduction in defense could come at the cost of increased infection susceptibility. We conducted common garden studies of the shore crab Hemigrapsus sanguineus from highly parasitized native (Japan) populations and largely parasite-free invasive (USA) populations to test for differences in susceptibility to infection by native-range rhizocephalan parasites, and to explore differences in host resource allocation. Nonnative individuals showed at least 1.8 times greater susceptibility to infection than their native counterparts, and had reduced standing metabolic rates, suggesting that less of their energy was spent on physiological self-maintenance. Our results support an indirect advantage to parasite escape via the relaxation of costly physiological defenses. However, this advantage comes at the cost of heightened susceptibility, a trade-off of parasite escape that is seldom considered. © 2017 by the Ecological Society of America.

  6. Factors contributing to the development of anaemia in Plasmodium falciparum malaria: what about drug-resistant parasites?

    Quashie, Neils Ben; Akanmori, Bartholomew D; Ofori-Adjei, David

    2006-01-01

    implicated in its pathogenesis. Since resolution of malaria restores erythropoiesis, we hypothesized that drug-resistant strains of Plasmodium falciparum would increase the risk of severe anaemia developing from initially uncomplicated malaria. Using both in vivo and in vitro drug-sensitivity tests we...... compared the prevalence of drug-resistant malaria between severe malarial anaemia SA and non-anaemic malaria NAM patients. Assessment of treatment outcome using the WHO in vivo criteria showed no significant difference in parasite resistance between the two groups. The mean parasite clearance time was also......-treatment blood levels of chloroquine did not differ much between the two groups. Findings from this study could not therefore implicate drug-resistant parasites in the pathogenesis of severe malarial anaemia....

  7. Sub-microscopic malaria cases and mixed malaria infection in a remote area of high malaria endemicity in Rattanakiri province, Cambodia: implication for malaria elimination

    Socheat Duong

    2010-04-01

    Full Text Available Abstract Background Malaria microscopy and rapid diagnostic tests are insensitive for very low-density parasitaemia. This insensitivity may lead to missed asymptomatic sub-microscopic parasitaemia, a potential reservoir for infection. Similarly, mixed infections and interactions between Plasmodium species may be missed. The objectives were first to develop a rapid and sensitive PCR-based diagnostic method to detect low parasitaemia and mixed infections, and then to investigate the epidemiological importance of sub-microscopic and mixed infections in Rattanakiri Province, Cambodia. Methods A new malaria diagnostic method, using restriction fragment length polymorphism analysis of the cytochrome b genes of the four human Plasmodium species and denaturing high performance liquid chromatography, has been developed. The results of this RFLP-dHPLC method have been compared to 1 traditional nested PCR amplification of the 18S rRNA gene, 2 sequencing of the amplified fragments of the cytochrome b gene and 3 microscopy. Blood spots on filter paper and Giemsa-stained blood thick smears collected in 2001 from 1,356 inhabitants of eight villages of Rattanakiri Province have been analysed by the RFLP-dHPLC method and microscopy to assess the prevalence of sub-microscopic and mixed infections. Results The sensitivity and specificity of the new RFLP-dHPLC was similar to that of the other molecular methods. The RFLP-dHPLC method was more sensitive and specific than microscopy, particularly for detecting low-level parasitaemia and mixed infections. In Rattanakiri Province, the prevalences of Plasmodium falciparum and Plasmodium vivax were approximately two-fold and three-fold higher, respectively, by RFLP-dHPLC (59% and 15%, respectively than by microscopy (28% and 5%, respectively. In addition, Plasmodium ovale and Plasmodium malariae were never detected by microscopy, while they were detected by RFLP-dHPLC, in 11.2% and 1.3% of the blood samples, respectively

  8. Bionomics of Anopheles latens in Kapit, Sarawak, Malaysian Borneo in relation to the transmission of zoonotic simian malaria parasite Plasmodium knowlesi

    Matusop Asmad

    2008-03-01

    Full Text Available Abstract Background A large focus of human infections with Plasmodium knowlesi, a simian parasite naturally found in long-tailed and pig-tailed macaques was discovered in the Kapit Division of Sarawak, Malaysian Borneo. A study was initiated to identify the vectors of malaria, to elucidate where transmission is taking place and to understand the bionomics of the vectors in Kapit. Methods Three different ecological sites in the forest, farm and longhouse in the Kapit district were selected for the study. Mosquitoes were collected by human landing collection at all sites and at the forest also by monkey-baited-traps situated on three different levels. All mosquitoes were identified and salivary glands and midguts of anopheline mosquitoes were dissected to determine the presence of malaria parasites. Results and Discussions Over an 11-month period, a total of 2,504 Anopheles mosquitoes comprising 12 species were caught; 1,035 at the farm, 774 at the forest and 425 at the longhouse. Anopheles latens (62.3% and Anopheles watsonii (30.6% were the predominant species caught in the forested ecotypes, while in the farm Anopheles donaldi (49.9% and An. latens (35.6% predominated. In the long house, An. latens (29.6% and An. donaldi (22.8% were the major Anopheline species. However, An. latens was the only mosquito positive for sporozoites and it was found to be attracted to both human and monkey hosts. In monkey-baited net traps, it preferred to bite monkeys at the canopy level than at ground level. An. latens was found biting early as 18.00 hours. Conclusion Anopheles latens is the main vector for P. knowlesi malaria parasites in the Kapit District of Sarawak, Malaysian Borneo. The study underscores the relationship between ecology, abundance and bionomics of anopheline fauna. The simio-anthropophagic and acrodendrophilic behaviour of An. latens makes it an efficient vector for the transmission of P. knowlesi parasites to both human and monkey hosts.

  9. Bionomics of Anopheles latens in Kapit, Sarawak, Malaysian Borneo in relation to the transmission of zoonotic simian malaria parasite Plasmodium knowlesi

    Tan, Cheong H; Vythilingam, Indra; Matusop, Asmad; Chan, Seng T; Singh, Balbir

    2008-01-01

    Background A large focus of human infections with Plasmodium knowlesi, a simian parasite naturally found in long-tailed and pig-tailed macaques was discovered in the Kapit Division of Sarawak, Malaysian Borneo. A study was initiated to identify the vectors of malaria, to elucidate where transmission is taking place and to understand the bionomics of the vectors in Kapit. Methods Three different ecological sites in the forest, farm and longhouse in the Kapit district were selected for the study. Mosquitoes were collected by human landing collection at all sites and at the forest also by monkey-baited-traps situated on three different levels. All mosquitoes were identified and salivary glands and midguts of anopheline mosquitoes were dissected to determine the presence of malaria parasites. Results and Discussions Over an 11-month period, a total of 2,504 Anopheles mosquitoes comprising 12 species were caught; 1,035 at the farm, 774 at the forest and 425 at the longhouse. Anopheles latens (62.3%) and Anopheles watsonii (30.6%) were the predominant species caught in the forested ecotypes, while in the farm Anopheles donaldi (49.9%) and An. latens (35.6%) predominated. In the long house, An. latens (29.6%) and An. donaldi (22.8%) were the major Anopheline species. However, An. latens was the only mosquito positive for sporozoites and it was found to be attracted to both human and monkey hosts. In monkey-baited net traps, it preferred to bite monkeys at the canopy level than at ground level. An. latens was found biting early as 18.00 hours. Conclusion Anopheles latens is the main vector for P. knowlesi malaria parasites in the Kapit District of Sarawak, Malaysian Borneo. The study underscores the relationship between ecology, abundance and bionomics of anopheline fauna. The simio-anthropophagic and acrodendrophilic behaviour of An. latens makes it an efficient vector for the transmission of P. knowlesi parasites to both human and monkey hosts. PMID:18377652

  10. Antisense long noncoding RNAs regulate var gene activation in the malaria parasite Plasmodium falciparum.

    Amit-Avraham, Inbar; Pozner, Guy; Eshar, Shiri; Fastman, Yair; Kolevzon, Netanel; Yavin, Eylon; Dzikowski, Ron

    2015-03-03

    The virulence of Plasmodium falciparum, the causative agent of the deadliest form of human malaria, is attributed to its ability to evade human immunity through antigenic variation. These parasites alternate between expression of variable antigens, encoded by members of a multicopy gene family named var. Immune evasion through antigenic variation depends on tight regulation of var gene expression, ensuring that only a single var gene is expressed at a time while the rest of the family is maintained transcriptionally silent. Understanding how a single gene is chosen for activation is critical for understanding mutually exclusive expression but remains a mystery. Here, we show that antisense long noncoding RNAs (lncRNAs) initiating from var introns are associated with the single active var gene at the time in the cell cycle when the single var upstream promoter is active. We demonstrate that these antisense transcripts are incorporated into chromatin, and that expression of these antisense lncRNAs in trans triggers activation of a silent var gene in a sequence- and dose-dependent manner. On the other hand, interference with these lncRNAs using complement peptide nucleic acid molecules down-regulated the active var gene, erased the epigenetic memory, and induced expression switching. Altogether, our data provide evidence that these antisense lncRNAs play a key role in regulating var gene activation and mutually exclusive expression.

  11. Immunoinformatics of Placental Malaria Vaccine Development

    Jessen, Leon Eyrich

    Malaria is an infectious disease caused by a protozoan parasite of the genus Plasmodium, which is transferred by female Anopheles mosquitos. WHO estimates that in 2012 there were 207 million cases of malaria, of which 627,000 were fatal. People living in malaria-endemic areas, gradually acquire...... immunity with multiple infections. Placental malaria (PM) is caused by P. falciparum sequestering in the placenta of pregnant women due to the presence of novel receptors in the placenta. An estimated 200,000 infants die a year as a result of PM. In 2004 the specific protein responsible...... and development in the field of placental malaria vaccine development....

  12. Identification of pre-erythrocytic malaria antigens that target hepatocytes for killing in vivo and contribute to protection elicited by whole-parasite vaccination.

    Lin Chen

    Full Text Available Pre-erythrocytic malaria vaccines, including those based on whole-parasite approaches, have shown protective efficacy in animal and human studies. However few pre-erythocytic antigens other than the immunodominant circumsporozoite protein (CSP have been studied in depth with the goal of developing potent subunit malaria vaccines that are suited for use in endemic areas. Here we describe a novel technique to identify pre-erythrocytic malaria antigens that contribute to protection elicited by whole-parasite vaccination in the mouse model. Our approach combines immunization with genetically attenuated parasites and challenge with DNA plasmids encoding for potential protective pre-erythrocytic malaria antigens as luciferase fusions by hydrodynamic tail vein injection. After optimizing the technique, we first showed that immunization with Pyfabb/f-, a P. yoelii genetically attenuated parasite, induces killing of CSP-presenting hepatocytes. Depletion of CD8+ but not CD4+ T cells diminished the killing of CSP-expressing hepatocytes, indicating that killing is CD8+ T cell-dependent. Finally we showed that the use of heterologous prime/boost immunization strategies that use genetically attenuated parasites and DNA vaccines enabled the characterization of a novel pre-erythrocytic antigen, Tmp21, as a contributor to Pyfabb/f- induced protection. This technique will be valuable for identification of potentially protective liver stage antigens and has the potential to contribute to the understanding of immunity elicited by whole parasite vaccination, as well as the development of effective subunit malaria vaccines.

  13. Malaria.

    Dupasquier, Isabelle

    1989-01-01

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

  14. Initial characterization of the Pf-Int recombinase from the malaria parasite Plasmodium falciparum.

    Mehdi Ghorbal

    Full Text Available Genetic variation is an essential means of evolution and adaptation in many organisms in response to environmental change. Certain DNA alterations can be carried out by site-specific recombinases (SSRs that fall into two families: the serine and the tyrosine recombinases. SSRs are seldom found in eukaryotes. A gene homologous to a tyrosine site-specific recombinase has been identified in the genome of Plasmodium falciparum. The sequence is highly conserved among five other members of Plasmodia.The predicted open reading frame encodes for a ∼57 kDa protein containing a C-terminal domain including the putative tyrosine recombinase conserved active site residues R-H-R-(H/W-Y. The N-terminus has the typical alpha-helical bundle and potentially a mixed alpha-beta domain resembling that of λ-Int. Pf-Int mRNA is expressed differentially during the P. falciparum erythrocytic life stages, peaking in the schizont stage. Recombinant Pf-Int and affinity chromatography of DNA from genomic or synthetic origin were used to identify potential DNA targets after sequencing or micro-array hybridization. Interestingly, the sequences captured also included highly variable subtelomeric genes such as var, rif, and stevor sequences. Electrophoretic mobility shift assays with DNA were carried out to verify Pf-Int/DNA binding. Finally, Pf-Int knock-out parasites were created in order to investigate the biological role of Pf-Int.Our data identify for the first time a malaria parasite gene with structural and functional features of recombinases. Pf-Int may bind to and alter DNA, either in a sequence specific or in a non-specific fashion, and may contribute to programmed or random DNA rearrangements. Pf-Int is the first molecular player identified with a potential role in genome plasticity in this pathogen. Finally, Pf-Int knock-out parasite is viable showing no detectable impact on blood stage development, which is compatible with such function.

  15. Malaria's missing number: calculating the human component of R0 by a within-host mechanistic model of Plasmodium falciparum infection and transmission.

    Geoffrey L Johnston

    2013-04-01

    Full Text Available Human infection by malarial parasites of the genus Plasmodium begins with the bite of an infected Anopheles mosquito. Current estimates place malaria mortality at over 650,000 individuals each year, mostly in African children. Efforts to reduce disease burden can benefit from the development of mathematical models of disease transmission. To date, however, comprehensive modeling of the parameters defining human infectivity to mosquitoes has remained elusive. Here, we describe a mechanistic within-host model of Plasmodium falciparum infection in humans and pathogen transmission to the mosquito vector. Our model incorporates the entire parasite lifecycle, including the intra-erythrocytic asexual forms responsible for disease, the onset of symptoms, the development and maturation of intra-erythrocytic gametocytes that are transmissible to Anopheles mosquitoes, and human-to-mosquito infectivity. These model components were parameterized from malaria therapy data and other studies to simulate individual infections, and the ensemble of outputs was found to reproduce the full range of patient responses to infection. Using this model, we assessed human infectivity over the course of untreated infections and examined the effects in relation to transmission intensity, expressed by the basic reproduction number R0 (defined as the number of secondary cases produced by a single typical infection in a completely susceptible population. Our studies predict that net human-to-mosquito infectivity from a single non-immune individual is on average equal to 32 fully infectious days. This estimate of mean infectivity is equivalent to calculating the human component of malarial R0 . We also predict that mean daily infectivity exceeds five percent for approximately 138 days. The mechanistic framework described herein, made available as stand-alone software, will enable investigators to conduct detailed studies into theories of malaria control, including the effects of

  16. Malaria and blood transfusion: major issues of blood safety in malaria-endemic countries and strategies for mitigating the risk of Plasmodium parasites.

    Abdullah, Saleh; Karunamoorthi, Kaliyaperumal

    2016-01-01

    Malaria inflicts humankind over centuries, and it remains as a major threat to both clinical medicine and public health worldwide. Though hemotherapy is a life-sustaining modality, it continues to be a possible source of disease transmission. Hence, hemovigilance is a matter of grave concern in the malaria-prone third-world countries. In order to pursue an effective research on hemovigilance, a comprehensive search has been conducted by using the premier academic-scientific databases, WHO documents, and English-language search engines. One hundred two appropriate articles were chosen for data extraction, with a particular reference to emerging pathogens transmitted through blood transfusion, specifically malaria. Blood donation screening is done through microscopic examination and immunological assays to improve the safety of blood products by detection major blood-borne pathogens, viz., HIV, HBV, HCV, syphilis, and malarial parasites. Transfusion therapy significantly dwindles the preventable morbidity and mortality attributed to various illnesses and diseases, particularly AIDS, tuberculosis, and malaria. Examination of thick and thin blood smears are performed to detect positivity and to identify the Plasmodium species, respectively. However, all of these existing diagnostic tools have their own limitations in terms of sensitivity, specificity, cost-effectiveness, and lack of resources and skilled personnel. Globally, despite the mandate need of screening blood and its components according to the blood-establishment protocols, it is seldom practiced in the low-income/poverty-stricken settings. In addition, each and every single phase of transfusion chain carries sizable inherent risks from donors to recipients. Interestingly, opportunities also lie ahead to enhance the safety of blood-supply chain and patients. It can be achieved through sustainable blood-management strategies like (1) appropriate usage of precise di