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Sample records for malaria transmission blocking

  1. Development of malaria transmission-blocking vaccines: from concept to product.

    PubMed

    Wu, Yimin; Sinden, Robert E; Churcher, Thomas S; Tsuboi, Takafumi; Yusibov, Vidadi

    2015-06-01

    Despite decades of effort battling against malaria, the disease is still a major cause of morbidity and mortality. Transmission-blocking vaccines (TBVs) that target sexual stage parasite development could be an integral part of measures for malaria elimination. In the 1950s, Huff et al. first demonstrated the induction of transmission-blocking immunity in chickens by repeated immunizations with Plasmodium gallinaceum-infected red blood cells. Since then, significant progress has been made in identification of parasite antigens responsible for transmission-blocking activity. Recombinant technologies accelerated evaluation of these antigens as vaccine candidates, and it is possible to induce effective transmission-blocking immunity in humans both by natural infection and now by immunization with recombinant vaccines. This chapter reviews the efforts to produce TBVs, summarizes the current status and advances and discusses the remaining challenges and approaches.

  2. A class of tricyclic compounds blocking malaria parasite oocyst development and transmission.

    PubMed

    Eastman, Richard T; Pattaradilokrat, Sittiporn; Raj, Dipak K; Dixit, Saurabh; Deng, Bingbing; Miura, Kazutoyo; Yuan, Jing; Tanaka, Takeshi Q; Johnson, Ronald L; Jiang, Hongying; Huang, Ruili; Williamson, Kim C; Lambert, Lynn E; Long, Carole; Austin, Christopher P; Wu, Yimin; Su, Xin-Zhuan

    2013-01-01

    Malaria is a deadly infectious disease in many tropical and subtropical countries. Previous efforts to eradicate malaria have failed, largely due to the emergence of drug-resistant parasites, insecticide-resistant mosquitoes and, in particular, the lack of drugs or vaccines to block parasite transmission. ATP-binding cassette (ABC) transporters are known to play a role in drug transport, metabolism, and resistance in many organisms, including malaria parasites. To investigate whether a Plasmodium falciparum ABC transporter (Pf14_0244 or PfABCG2) modulates parasite susceptibility to chemical compounds or plays a role in drug resistance, we disrupted the gene encoding PfABCG2, screened the recombinant and the wild-type 3D7 parasites against a library containing 2,816 drugs approved for human or animal use, and identified an antihistamine (ketotifen) that became less active against the PfABCG2-disrupted parasite in culture. In addition to some activity against asexual stages and gametocytes, ketotifen was highly potent in blocking oocyst development of P. falciparum and the rodent parasite Plasmodium yoelii in mosquitoes. Tests of structurally related tricyclic compounds identified additional compounds with similar activities in inhibiting transmission. Additionally, ketotifen appeared to have some activity against relapse of Plasmodium cynomolgi infection in rhesus monkeys. Further clinical evaluation of ketotifen and related compounds, including synthetic new derivatives, in blocking malaria transmission may provide new weapons for the current effort of malaria eradication.

  3. Toward the development of effective transmission-blocking vaccines for malaria.

    PubMed

    Nikolaeva, Daria; Draper, Simon J; Biswas, Sumi

    2015-05-01

    The continued global burden of malaria can in part be attributed to a complex lifecycle, with both human hosts and mosquito vectors serving as transmission reservoirs. In preclinical models of vaccine-induced immunity, antibodies to parasite sexual-stage antigens, ingested in the mosquito blood meal, can inhibit parasite survival in the insect midgut as judged by ex vivo functional studies such as the membrane feeding assay. In an era of renewed political momentum for malaria elimination and eradication campaigns, such observations have fueled support for the development and implementation of so-called transmission-blocking vaccines. While leading candidates are being evaluated using a variety of promising vaccine platforms, the field is also beginning to capitalize on global '-omics' data for the rational genome-based selection and unbiased characterization of parasite and mosquito proteins to expand the candidate list. This review covers the progress and prospects of these recent developments.

  4. Development of a Pfs25-EPA malaria transmission blocking vaccine as a chemically conjugated nanoparticle.

    PubMed

    Shimp, Richard L; Rowe, Christopher; Reiter, Karine; Chen, Beth; Nguyen, Vu; Aebig, Joan; Rausch, Kelly M; Kumar, Krishan; Wu, Yimin; Jin, Albert J; Jones, David S; Narum, David L

    2013-06-19

    Successful efforts to control infectious diseases have often required the use of effective vaccines. The current global strategy for control of malaria, including elimination and eradication will also benefit from the development of an effective vaccine that interrupts malaria transmission. To this end, a vaccine that disrupts malaria transmission within the mosquito host has been investigated for several decades targeting a 25 kDa ookinete specific surface protein, identified as Pfs25. Phase 1 human trial results using a recombinant Pfs25H/Montanide ISA51 formulation demonstrated that human Pfs25 specific antibodies block parasite infectivity to mosquitoes; however, the extent of blocking was likely insufficient for an effective transmission blocking vaccine. To overcome the poor immunogenicity, processes to produce and characterize recombinant Pfs25H conjugated to a detoxified form of Pseudomonas aeruginosa exoprotein A (EPA) have been developed and used to manufacture a cGMP pilot lot for use in human clinical trials. The Pfs25-EPA conjugate appears as a nanoparticle with an average molar mass in solution of approximately 600 kDa by static light scattering with an average diameter 20 nm (range 10-40 nm) by dynamic light scattering. The molar ratio of Pfs25H to EPA is about 3 to 1 by amino acid analysis, respectively. Outbred mice immunized with the Pfs25-EPA conjugated nanoparticle formulated on Alhydrogel(®) had a 75-110 fold increase in Pfs25H specific antibodies when compared to an unconjugated Pfs25H/Alhydrogel(®) formulation. A phase 1 human trial using the Pfs25-EPA/Alhydrogel(®) formulation is ongoing in the United States.

  5. Development of a Pfs25-EPA malaria transmission blocking vaccine as a chemically conjugated nanoparticle

    PubMed Central

    Shimp, Richard L.; Rowe, Christopher; Reiter, Karine; Chen, Beth; Nguyen, Vu; Aebig, Joan; Rausch, Kelly M.; Kumar, Krishan; Wu, Yimin; Jin, Albert J.; Jones, David S.; Narum, David L.

    2013-01-01

    Successful efforts to control infectious diseases have often required the use of effective vaccines. The current global strategy for control of malaria, including elimination and eradication will also benefit from the development of an effective vaccine that interrupts malaria transmission. To this end, a vaccine that disrupts malaria transmission within the mosquito host has been investigated for several decades targeting a 25 kDa ookinete specific surface protein, identified as Pfs25. Phase 1 human trial results using a recombinant Pfs25H/Montanide ISA51 formulation demonstrated that human Pfs25 specific antibodies block parasite infectivity to mosquitoes; however, the extent of blocking was likely insufficient for an effective transmission blocking vaccine. To overcome the poor immunogenicity, processes to produce and characterize recombinant Pfs25H conjugated to a detoxified form of Pseudomonas aeruginosa exoprotein A (EPA) have been developed and used to manufacture a cGMP pilot lot for use in human clinical trials. The Pfs25-EPA conjugate appears as a nanoparticle with an average molar mass in solution of approximately 600 kDa by static light scattering with an average diameter 20 nm (range 10 to 40 nm) by dynamic light scattering. The molar ratio of Pfs25H to EPA is about 3 to 1 by amino acid analysis, respectively. Outbred mice immunized with the Pfs25-EPA conjugated nanoparticle formulated on Alhydrogel® had a 75 to 110 fold increase in Pfs25H specific antibodies when compared to an unconjugated Pfs25H/Alhydrogel® formulation. A phase 1 human trial using the Pfs25-EPA/Alhydrogel® formulation is ongoing in the United States. PMID:23623858

  6. Splenic Retention of Plasmodium falciparum Gametocytes To Block the Transmission of Malaria

    PubMed Central

    Duez, Julien; Holleran, John P.; Ndour, Papa Alioune; Loganathan, Sasdekumar; Amireault, Pascal; Français, Olivier; El Nemer, Wassim; Le Pioufle, Bruno; Amado, Inês F.; Garcia, Sylvie; Chartrel, Nathalie; Le Van Kim, Caroline; Lavazec, Catherine; Avery, Vicky M.

    2015-01-01

    Plasmodium falciparum is transmitted from humans to Anopheles mosquito vectors via the sexual erythrocytic forms termed gametocytes. Erythrocyte filtration through microsphere layers (microsphiltration) had shown that circulating gametocytes are deformable. Compounds reducing gametocyte deformability would induce their splenic clearance, thus removing them from the blood circulation and blocking malaria transmission. The hand-made, single-sample prototype for microsphiltration was miniaturized to a 96-well microtiter plate format, and gametocyte retention in the microsphere filters was quantified by high-content imaging. The stiffening activity of 40 pharmacological compounds was assessed in microtiter plates, using a small molecule (calyculin) as a positive control. The stiffening activity of calyculin was assessed in spleen-mimetic microfluidic chips and in macrophage-depleted mice. Marked mechanical retention (80% to 90%) of mature gametocytes was obtained in microplates following exposure to calyculin at concentrations with no effect on parasite viability. Of the 40 compounds tested, including 20 antimalarials, only 5 endoperoxides significantly increased gametocyte retention (1.5- to 2.5-fold; 24 h of exposure at 1 μM). Mature gametocytes exposed to calyculin accumulated in microfluidic chips and were cleared from the circulation of macrophage-depleted mice as rapidly as heat-stiffened erythrocytes, thus confirming results obtained using the microsphiltration assay. An automated miniaturized approach to select compounds for their gametocyte-stiffening effect has been established. Stiffening induces gametocyte clearance both in vitro and in vivo. Based on physiologically validated tools, this screening cascade can identify novel compounds and uncover new targets to block malaria transmission. Innovative applications in hematology are also envisioned. PMID:25941228

  7. Blocking Plasmodium falciparum Malaria Transmission with Drugs: The Gametocytocidal and Sporontocidal Properties of Current and Prospective Antimalarials

    PubMed Central

    Kiszewski, Anthony E.

    2011-01-01

    Drugs that kill or inhibit the sexual stages of Plasmodium could potentially amplify or synergize the impact of other interventions by blocking transmission to mosquitoes. Primaquine and other 8-aminoquinolines have long offered such potential, but safety and other concerns have limited their use. Although transmission-blocking properties are not often a priority of drug discovery efforts, a number of interesting gametocytocidal and/or sporontocidal drug candidates have emerged in recent years. Some still bear significant technical and safety concerns, while others have passed clinical trials and are on the verge of entering the antimalarial armamentarium. Recent advances in our knowledge of gametocyte differentiation, gametogenesis and sporogony have also led to the identification of a large array of potential new targets for drugs that might interfere with malaria transmission. This review examines the properties of existing and prospective drugs, mechanisms of action, counter-indications and their potential role in regional malaria elimination efforts.

  8. Enzymatic characterization of the Plasmodium vivax chitinase, a potential malaria transmission-blocking target

    PubMed Central

    Takeo, Satoru; Hisamori, Daisuke; Matsuda, Shusaku; Vinetz, Joseph; Sattabongkot, Jetsumon; Tsuboi, Takafumi

    2009-01-01

    The chitinase (EC 3.2.1.14) of the human malaria parasite Plasmodium falciparum, PfCHT1, has been validated as a malaria transmission-blocking vaccine (TBV). The present study aimed to delineate functional characteristics of the P. vivax chitinase PvCHT1, whose primary structure differs from that of PfCHT1 by having proenzyme and chitin-binding domains. The recombinant protein rPvCHT1 expressed with a wheat germ cell-free system hydrolyzed 4-methylumbelliferone (4MU) derivatives of chitin oligosaccharides (β-1,4-poly-N-acetyl glucosamine (GlcNAc)). An anti-rPvCHT1 polyclonal antiserum reacted with in vitro-obtained P. vivax ookinetes in anterior cytoplasm, showing uneven patchy distribution. Enzymatic activity of rPvCHT1 shared the exclusive endochitinase property with parallelly expressed rPfCHT1 as demonstrated by a marked substrate preference for 4MU-GlcNAc3 compared to shorter GlcNAc substrates. While rPvCHT1 was found to be sensitive to the general family-18 chitinase inhibitor, allosamidin, its pH (maximal in neutral environment) and temperature (max. at ~25 °C) activity profiles and sensitivity to allosamidin (IC50=6 μM) were different from rPfCHT1. The results in this first report of functional rPvCHT1 synthesis indicate that the P. vivax chitinase is enzymatically close to long form Plasmodium chitinases represented by P. gallinaceum PgCHT1. PMID:19427918

  9. Cloning, expression and transmission-blocking activity of anti-PvWARP, malaria vaccine candidate, in Anopheles stephensi mysorensis

    PubMed Central

    2010-01-01

    Background Notwithstanding progress in recent years, a safe, an effective and affordable malaria vaccine is not available yet. Ookinete-secreted protein, Plasmodium vivax von Willebrand factor A domain-related protein (PvWARP), is a candidate for malaria transmission-blocking vaccines (TBVs). Methods The PvWARP was expressed in Escherichia coli BL21 using the pET-23a vector and was purified using Ni-NTA affinity chromatography from a soluble fraction. Polyclonal antibody was raised against rPvWARP and transmission blocking activity was carried out in an Anopheles stephensi-P. vivax model. Results Expression of full length of PvWARP (minus signal peptide) expression showed a 35-kDa protein. The purified protein was recognized by mouse polyclonal antibody directed against rPvWARP. Sera from the animals displayed significantly a blocking activity in the membrane feeding assay of An. stephensi mysorensis. Conclusions This is the first report on P. vivax WARP expression in E. coli that provides an essential base for development of the malaria TBV against P. vivax. This may greatly assist in malaria elimination, especially in the oriental corner of WHO Eastern Mediterranean Regional Office (WHO/EMRO) including Afghanistan, Iran and Pakistan. PMID:20537198

  10. Recombinant Pvs48/45 Antigen Expressed in E. coli Generates Antibodies that Block Malaria Transmission in Anopheles albimanus Mosquitoes

    PubMed Central

    Arévalo-Herrera, Myriam; Vallejo, Andrés F.; Rubiano, Kelly; Solarte, Yezid; Marin, Catherin; Castellanos, Angélica; Céspedes, Nora; Herrera, Sócrates

    2015-01-01

    Transmission of malaria parasites from humans to Anopheles mosquitoes can be inhibited by specific antibodies elicited during malaria infection, which target surface Plasmodium gametocyte/gamete proteins. Some of these proteins may have potential for vaccine development. Pvs48/45 is a P. vivax gametocyte surface antigen orthologous to Pfs48/45, which may play a role during parasite fertilization and thus has potential for transmission blocking (TB) activity. Here we describe the expression of a recombinant Pvs48/45 protein expressed in Escherichia coli as a ∼60kDa construct which we tested for antigenicity using human sera and for its immunogenicity and transmission blocking activity of specific anti-mouse and anti-monkey Pvs48/45 antibodies. The protein reacted with sera of individuals from malaria-endemic areas and in addition induced specific IgG antibody responses in BALB/c mice and Aotus l. griseimembra monkeys. Sera from both immunized animal species recognized native P. vivax protein in Western blot (WB) and immunofluorescence assays. Moreover, sera from immunized mice and monkeys produced significant inhibition of parasite transmission to An. Albimanus mosquitoes as shown by membrane feeding assays. Results indicate the presence of reactive epitopes in the Pvs48/45 recombinant product that induce antibodies with TB activity. Further testing of this protein is ongoing to determine its vaccine potential. PMID:25775466

  11. Recombinant Pvs48/45 antigen expressed in E. coli generates antibodies that block malaria transmission in Anopheles albimanus mosquitoes.

    PubMed

    Arévalo-Herrera, Myriam; Vallejo, Andrés F; Rubiano, Kelly; Solarte, Yezid; Marin, Catherin; Castellanos, Angélica; Céspedes, Nora; Herrera, Sócrates

    2015-01-01

    Transmission of malaria parasites from humans to Anopheles mosquitoes can be inhibited by specific antibodies elicited during malaria infection, which target surface Plasmodium gametocyte/gamete proteins. Some of these proteins may have potential for vaccine development. Pvs48/45 is a P. vivax gametocyte surface antigen orthologous to Pfs48/45, which may play a role during parasite fertilization and thus has potential for transmission blocking (TB) activity. Here we describe the expression of a recombinant Pvs48/45 protein expressed in Escherichia coli as a ∼60kDa construct which we tested for antigenicity using human sera and for its immunogenicity and transmission blocking activity of specific anti-mouse and anti-monkey Pvs48/45 antibodies. The protein reacted with sera of individuals from malaria-endemic areas and in addition induced specific IgG antibody responses in BALB/c mice and Aotus l. griseimembra monkeys. Sera from both immunized animal species recognized native P. vivax protein in Western blot (WB) and immunofluorescence assays. Moreover, sera from immunized mice and monkeys produced significant inhibition of parasite transmission to An. Albimanus mosquitoes as shown by membrane feeding assays. Results indicate the presence of reactive epitopes in the Pvs48/45 recombinant product that induce antibodies with TB activity. Further testing of this protein is ongoing to determine its vaccine potential.

  12. Correctly folded Pfs48/45 protein of Plasmodium falciparum elicits malaria transmission-blocking immunity in mice

    PubMed Central

    Outchkourov, Nikolay S.; Roeffen, Will; Kaan, Anita; Jansen, Josephine; Luty, Adrian; Schuiffel, Danielle; van Gemert, Geert Jan; van de Vegte-Bolmer, Marga; Sauerwein, Robert W.; Stunnenberg, Hendrik G.

    2008-01-01

    Malaria kills >1 million people each year, in particular in sub-Saharan Africa. Although asexual forms are directly responsible for disease and death, sexual stages account for the transmission of Plasmodium parasites from human to the mosquito vector and therefore the spread of the parasite in the population. Development of a malaria vaccine is urgently needed to reduce morbidity and mortality. Vaccines against sexual stages of Plasmodium falciparum are meant to decrease the force of transmission and consequently reduce malaria burden. Pfs48/45 is specifically expressed in sexual stages and is a well established transmission-blocking (TB) vaccine candidate. However, production of correctly folded recombinant Pfs48/45 protein with display of its TB epitopes has been a major challenge. Here, we show the production of a properly folded Pfs48/45 C-terminal fragment by simultaneous coexpression with four periplasmic folding catalysts in Escherichia coli. This C-terminal fragment fused to maltose binding protein was produced at medium scale with >90% purity and a stability over at least a 9-month period. It induces uniform and high antibody titers in mice and elicits functional TB antibodies in standard membrane feeding assays in 90% of the immunized mice. Our data provide a clear perspective on the clinical development of a Pfs48/45-based TB malaria vaccine. PMID:18332422

  13. Enhancing immunogenicity and transmission-blocking activity of malaria vaccines by fusing Pfs25 to IMX313 multimerization technology

    PubMed Central

    Li, Yuanyuan; Leneghan, Darren B.; Miura, Kazutoyo; Nikolaeva, Daria; Brian, Iona J.; Dicks, Matthew D. J.; Fyfe, Alex J.; Zakutansky, Sarah E.; de Cassan, Simone; Long, Carole A.; Draper, Simon J.; Hill, Adrian V. S.; Hill, Fergal; Biswas, Sumi

    2016-01-01

    Transmission-blocking vaccines (TBV) target the sexual-stages of the malaria parasite in the mosquito midgut and are widely considered to be an essential tool for malaria elimination. High-titer functional antibodies are required against target antigens to achieve effective transmission-blocking activity. We have fused Pfs25, the leading malaria TBV candidate antigen to IMX313, a molecular adjuvant and expressed it both in ChAd63 and MVA viral vectors and as a secreted protein-nanoparticle. Pfs25-IMX313 expressed from viral vectors or as a protein-nanoparticle is significantly more immunogenic and gives significantly better transmission-reducing activity than monomeric Pfs25. In addition, we demonstrate that the Pfs25-IMX313 protein-nanoparticle leads to a qualitatively improved antibody response in comparison to soluble Pfs25, as well as to significantly higher germinal centre (GC) responses. These results demonstrate that antigen multimerization using IMX313 is a very promising strategy to enhance antibody responses against Pfs25, and that Pfs25-IMX313 is a highly promising TBV candidate vaccine. PMID:26743316

  14. Enhancing immunogenicity and transmission-blocking activity of malaria vaccines by fusing Pfs25 to IMX313 multimerization technology.

    PubMed

    Li, Yuanyuan; Leneghan, Darren B; Miura, Kazutoyo; Nikolaeva, Daria; Brian, Iona J; Dicks, Matthew D J; Fyfe, Alex J; Zakutansky, Sarah E; de Cassan, Simone; Long, Carole A; Draper, Simon J; Hill, Adrian V S; Hill, Fergal; Biswas, Sumi

    2016-01-08

    Transmission-blocking vaccines (TBV) target the sexual-stages of the malaria parasite in the mosquito midgut and are widely considered to be an essential tool for malaria elimination. High-titer functional antibodies are required against target antigens to achieve effective transmission-blocking activity. We have fused Pfs25, the leading malaria TBV candidate antigen to IMX313, a molecular adjuvant and expressed it both in ChAd63 and MVA viral vectors and as a secreted protein-nanoparticle. Pfs25-IMX313 expressed from viral vectors or as a protein-nanoparticle is significantly more immunogenic and gives significantly better transmission-reducing activity than monomeric Pfs25. In addition, we demonstrate that the Pfs25-IMX313 protein-nanoparticle leads to a qualitatively improved antibody response in comparison to soluble Pfs25, as well as to significantly higher germinal centre (GC) responses. These results demonstrate that antigen multimerization using IMX313 is a very promising strategy to enhance antibody responses against Pfs25, and that Pfs25-IMX313 is a highly promising TBV candidate vaccine.

  15. Single-dose microparticle delivery of a malaria transmission-blocking vaccine elicits a long-lasting functional antibody response.

    PubMed

    Dinglasan, R R; Armistead, J S; Nyland, J F; Jiang, X; Mao, H Q

    2013-05-01

    Malaria sexual stage and mosquito transmission-blocking vaccines (SSM-TBV) have recently gained prominence as a necessary tool for malaria eradication. SSM-TBVs are unique in that, with the exception of parasite gametocyte antigens, they primarily target parasite or mosquito midgut surface antigens expressed only inside the mosquito. As such, the primary perceived limitation of SSM-TBVs is that the absence of natural boosting following immunization will limit its efficacy, since the antigens are never presented to the human immune system. An ideal, safe SSM-TBV formulation must overcome this limitation. We provide a focused evaluation of relevant nano-/microparticle technologies that can be applied toward the development of leading SSM-TBV candidates, and data from a proof-of-concept study demonstrating that a single inoculation and controlled release of antigen in mice, can elicit long-lasting protective antibody titers. We conclude by identifying the remaining critical gaps in knowledge and opportunities for moving SSM-TBVs to the field.

  16. Design of a Phase III cluster randomized trial to assess the efficacy and safety of a malaria transmission blocking vaccine.

    PubMed

    Delrieu, Isabelle; Leboulleux, Didier; Ivinson, Karen; Gessner, Bradford D

    2015-03-24

    Vaccines interrupting Plasmodium falciparum malaria transmission targeting sexual, sporogonic, or mosquito-stage antigens (SSM-VIMT) are currently under development to reduce malaria transmission. An international group of malaria experts was established to evaluate the feasibility and optimal design of a Phase III cluster randomized trial (CRT) that could support regulatory review and approval of an SSM-VIMT. The consensus design is a CRT with a sentinel population randomly selected from defined inner and buffer zones in each cluster, a cluster size sufficient to assess true vaccine efficacy in the inner zone, and inclusion of ongoing assessment of vaccine impact stratified by distance of residence from the cluster edge. Trials should be conducted first in areas of moderate transmission, where SSM-VIMT impact should be greatest. Sample size estimates suggest that such a trial is feasible, and within the range of previously supported trials of malaria interventions, although substantial issues to implementation exist.

  17. Using infections to fight infections: paratransgenic fungi can block malaria transmission in mosquitoes.

    PubMed

    Rasgon, Jason L

    2011-08-01

    EVALUATION OF: Fang W, Vega-Rodríguez J, Ghosh AK et al. Development of transgenic fungi that kill human malaria parasites in mosquitoes. Science 331(6020), 1074-1077 (2011). Paratransgenesis is the genetic manipulation of insect endosymbiotic microorganisms such as bacteria, viruses or fungi. Paratransgenesis has been proposed as a potential method to control vector-borne diseases such as malaria. In this article, Fang and colleagues have used genetic manipulation to insert multiple antimalaria effector genes into the entomopathogenic fungus Metarhizium anisopliae. When the modified fungus was used to infect Anopheles mosquitoes, it expressed the antimalaria effector molecules in the mosquito hemolymph. When several different effector molecules were coexpressed, malaria levels in the mosquito salivary glands were inhibited by up to 98% compared with controls. Significant inhibition could be initiated by as little as seven fungal spores and was very rapid and long lasting. These data suggest that recombinant entomopathogenic fungi could be deployed as part of a strategy to control malaria.

  18. N-Terminal Prodomain of Pfs230 Synthesized Using a Cell-Free System Is Sufficient To Induce Complement-Dependent Malaria Transmission-Blocking Activity▿

    PubMed Central

    Tachibana, Mayumi; Wu, Yimin; Iriko, Hideyuki; Muratova, Olga; MacDonald, Nicholas J.; Sattabongkot, Jetsumon; Takeo, Satoru; Otsuki, Hitoshi; Torii, Motomi; Tsuboi, Takafumi

    2011-01-01

    The aim of a malaria transmission-blocking vaccine is to block the development of malaria parasites in the mosquito and thus prevent subsequent infection of the human host. Previous studies have demonstrated that the gametocyte/gamete surface protein Pfs230 can induce transmission-blocking immunity and have evaluated Escherichia coli-produced Pfs230 as a transmission-blocking vaccine candidate. In this study, we used the wheat germ cell-free expression system to produce N-terminal fragments of Pfs230 and evaluated the transmission-blocking activity of antisera raised against the recombinant Pfs230 protein. The rabbit antisera reacted to the surface of cultured gametocytes and gametes of the Plasmodium falciparum NF54 line, recognized the 360-kDa form of parasite-produced Pfs230 by Western blot assay, and reduced the infectivity of NF54 parasites to Anopheles stefensi mosquitoes in the presence of complement in a standard membrane feeding assay. Thus, our data demonstrate that the N-terminal pro domain of Pfs230 is sufficient to induce complement-dependent transmission-blocking activity against P. falciparum. PMID:21715579

  19. Heat-precipitation allows the efficient purification of a functional plant-derived malaria transmission-blocking vaccine candidate fusion protein.

    PubMed

    Beiss, Veronique; Spiegel, Holger; Boes, Alexander; Kapelski, Stephanie; Scheuermayer, Matthias; Edgue, Gueven; Sack, Markus; Fendel, Rolf; Reimann, Andreas; Schillberg, Stefan; Pradel, Gabriele; Fischer, Rainer

    2015-07-01

    Malaria is a vector-borne disease affecting more than two million people and accounting for more than 600,000 deaths each year, especially in developing countries. The most serious form of malaria is caused by Plasmodium falciparum. The complex life cycle of this parasite, involving pre-erythrocytic, asexual and sexual stages, makes vaccine development cumbersome but also offers a broad spectrum of vaccine candidates targeting exactly those stages. Vaccines targeting the sexual stage of P. falciparum are called transmission-blocking vaccines (TBVs). They do not confer protection for the vaccinated individual but aim to reduce or prevent the transmission of the parasite within a population and are therefore regarded as an essential tool in the fight against the disease. Malaria predominantly affects large populations in developing countries, so TBVs need to be produced in large quantities at low cost. Combining the advantages of eukaryotic expression with a virtually unlimited upscaling potential and a good product safety profile, plant-based expression systems represent a suitable alternative for the production of TBVs. We report here the high level (300 μg/g fresh leaf weight (FLW)) transient expression in Nicotiana benthamiana leaves of an effective TBV candidate based on a fusion protein F0 comprising Pfs25 and the C0-domain of Pfs230, and the implementation of a simple and cost-effective heat treatment step for purification that yields intact recombinant protein at >90% purity with a recovery rate of >70%. The immunization of mice clearly showed that antibodies raised against plant-derived F0 completely blocked the formation of oocysts in a malaria transmission-blocking assay (TBA) making F0 an interesting TBV candidate or a component of a multi-stage malaria vaccine cocktail.

  20. Development of Potent and Selective Plasmodium falciparum Calcium-Dependent Protein Kinase 4 (PfCDPK4) Inhibitors that Block the Transmission of Malaria to Mosquitoes

    PubMed Central

    Vidadala, Rama Subba Rao; Ojo, Kayode K.; Johnson, Steven M.; Zhang, Zhongsheng; Leonard, Stephen E.; Mitra, Arinjay; Choi, Ryan; Reid, Molly C.; Keyloun, Katelyn R.; Fox, Anna M.W.; Kennedy, Mark; Silver-Brace, Tiffany; Hume, Jen C. C.; Kappe, Stefan; Verlinde, Christophe L.M.J.; Fan, Erkang; Merritt, Ethan A.; Van Voorhis, Wesley C.; Maly, Dustin J.

    2014-01-01

    Malaria remains a major health concern for a large percentage of the world’s population. While great strides have been made in reducing mortality due to malaria, new strategies and therapies are still needed. Therapies that are capable of blocking the transmission of Plasmodium parasites are particularly attractive, but only primaquine accomplishes this, and toxicity issues hamper its widespread use. In this study, we describe a series of pyrazolopyrimidine- and imidazopyrazine-based compounds that are potent inhibitors of PfCDPK4, which is a calcium-activated Plasmodium protein kinase that is essential for exflagellation of male gametocytes. Thus, PfCDPK4 is essential for the sexual development of Plasmodium parasites and their ability to infect mosquitos. We demonstrate that two structural features in the ATP-binding site of PfCDPK4 can be exploited in order to obtain potent and selective inhibitors of this enzyme. Furthermore, we demonstrate that pyrazolopyrimidine-based inhibitors that are potent inhibitors of the in vitro activity of PfCDPK4 are also able to block P. falciparum exflagellation with no observable toxicity to human cells. This medicinal chemistry effort serves as a valuable starting point in the development of safe, transmission-blocking agents for the control of malaria. PMID:24531197

  1. A simple and predictive phenotypic High Content Imaging assay for Plasmodium falciparum mature gametocytes to identify malaria transmission blocking compounds

    PubMed Central

    Lucantoni, Leonardo; Silvestrini, Francesco; Signore, Michele; Siciliano, Giulia; Eldering, Maarten; Dechering, Koen J.; Avery, Vicky M.; Alano, Pietro

    2015-01-01

    Plasmodium falciparum gametocytes, specifically the mature stages, are the only malaria parasite stage in humans transmissible to the mosquito vector. Anti-malarial drugs capable of killing these forms are considered essential for the eradication of malaria and tools allowing the screening of large compound libraries with high predictive power are needed to identify new candidates. As gametocytes are not a replicative stage it is difficult to apply the same drug screening methods used for asexual stages. Here we propose an assay, based on high content imaging, combining “classic” gametocyte viability readout based on gametocyte counts with a functional viability readout, based on gametocyte activation and the discrimination of the typical gamete spherical morphology. This simple and rapid assay has been miniaturized to a 384-well format using acridine orange staining of wild type P. falciparum 3D7A sexual forms, and was validated by screening reference antimalarial drugs and the MMV Malaria Box. The assay demonstrated excellent robustness and ability to identify quality hits with high likelihood of confirmation of transmission reducing activity in subsequent mosquito membrane feeding assays. PMID:26553647

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

    PubMed Central

    2010-01-01

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

  3. Safety and Immunogenicity of Pfs25-EPA/Alhydrogel®, a Transmission Blocking Vaccine against Plasmodium falciparum: An Open Label Study in Malaria Naïve Adults

    PubMed Central

    Talaat, Kawsar R.; Ellis, Ruth D.; Hurd, Janet; Hentrich, Autumn; Gabriel, Erin; Hynes, Noreen A.; Rausch, Kelly M.; Zhu, Daming; Muratova, Olga; Herrera, Raul; Anderson, Charles; Jones, David; Aebig, Joan; Brockley, Sarah; MacDonald, Nicholas J.; Wang, Xiaowei; Fay, Michael P.; Healy, Sara A.; Durbin, Anna P.; Narum, David L.; Wu, Yimin; Duffy, Patrick E.

    2016-01-01

    Transmission-blocking vaccines (TBVs) that target sexual stage parasite development could be an integral part of measures for malaria elimination. Pfs25 is a leading TBV candidate, and previous studies conducted in animals demonstrated an improvement of its functional immunogenicity after conjugation to EPA, a recombinant, detoxified ExoProtein A from Pseudomonas aeruginosa. In this report, we describe results of an open-label, dose-escalating Phase 1 trial to assess the safety and immunogenicity of Pfs25-EPA conjugates formulated with Alhydrogel®. Thirty malaria-naïve healthy adults received up to four doses of the conjugate vaccine, with 8, 16, or 47 μg of conjugated Pfs25 mass, at 0, 2, 4, and 10 months. Vaccinations were generally well tolerated. The majority of solicited adverse events were mild in severity with pain at the injection site the most common complaint. Anemia was the most common laboratory abnormality, but was considered possibly related to the study in only a minority of cases. No vaccine-related serious adverse events occurred. The peak geometric mean anti-Pfs25 antibody level in the highest dose group was 88 (95% CI 53, 147) μg/mL two weeks after the 4th vaccination, and declined to near baseline one year later. Antibody avidity increased over successive vaccinations. Transmission blocking activity demonstrated in a standard membrane feeding assay (SMFA) also increased from the second to the third dose, and correlated with antibody titer and, after the final dose, with antibody avidity. These results support the further evaluation of Pfs25-EPA/Alhydrogel® in a malaria-endemic population. PMID:27749907

  4. Safety and Immunogenicity of Pfs25-EPA/Alhydrogel®, a Transmission Blocking Vaccine against Plasmodium falciparum: An Open Label Study in Malaria Naïve Adults.

    PubMed

    Talaat, Kawsar R; Ellis, Ruth D; Hurd, Janet; Hentrich, Autumn; Gabriel, Erin; Hynes, Noreen A; Rausch, Kelly M; Zhu, Daming; Muratova, Olga; Herrera, Raul; Anderson, Charles; Jones, David; Aebig, Joan; Brockley, Sarah; MacDonald, Nicholas J; Wang, Xiaowei; Fay, Michael P; Healy, Sara A; Durbin, Anna P; Narum, David L; Wu, Yimin; Duffy, Patrick E

    2016-01-01

    Transmission-blocking vaccines (TBVs) that target sexual stage parasite development could be an integral part of measures for malaria elimination. Pfs25 is a leading TBV candidate, and previous studies conducted in animals demonstrated an improvement of its functional immunogenicity after conjugation to EPA, a recombinant, detoxified ExoProtein A from Pseudomonas aeruginosa. In this report, we describe results of an open-label, dose-escalating Phase 1 trial to assess the safety and immunogenicity of Pfs25-EPA conjugates formulated with Alhydrogel®. Thirty malaria-naïve healthy adults received up to four doses of the conjugate vaccine, with 8, 16, or 47 μg of conjugated Pfs25 mass, at 0, 2, 4, and 10 months. Vaccinations were generally well tolerated. The majority of solicited adverse events were mild in severity with pain at the injection site the most common complaint. Anemia was the most common laboratory abnormality, but was considered possibly related to the study in only a minority of cases. No vaccine-related serious adverse events occurred. The peak geometric mean anti-Pfs25 antibody level in the highest dose group was 88 (95% CI 53, 147) μg/mL two weeks after the 4th vaccination, and declined to near baseline one year later. Antibody avidity increased over successive vaccinations. Transmission blocking activity demonstrated in a standard membrane feeding assay (SMFA) also increased from the second to the third dose, and correlated with antibody titer and, after the final dose, with antibody avidity. These results support the further evaluation of Pfs25-EPA/Alhydrogel® in a malaria-endemic population.

  5. Malaria transmission rates estimated from serological data.

    PubMed Central

    Burattini, M. N.; Massad, E.; Coutinho, F. A.

    1993-01-01

    A mathematical model was used to estimate malaria transmission rates based on serological data. The model is minimally stochastic and assumes an age-dependent force of infection for malaria. The transmission rates estimated were applied to a simple compartmental model in order to mimic the malaria transmission. The model has shown a good retrieving capacity for serological and parasite prevalence data. PMID:8270011

  6. Mapping residual transmission for malaria elimination.

    PubMed

    Reiner, Robert C; Le Menach, Arnaud; Kunene, Simon; Ntshalintshali, Nyasatu; Hsiang, Michelle S; Perkins, T Alex; Greenhouse, Bryan; Tatem, Andrew J; Cohen, Justin M; Smith, David L

    2015-12-29

    Eliminating malaria from a defined region involves draining the endemic parasite reservoir and minimizing local malaria transmission around imported malaria infections . In the last phases of malaria elimination, as universal interventions reap diminishing marginal returns, national resources must become increasingly devoted to identifying where residual transmission is occurring. The needs for accurate measures of progress and practical advice about how to allocate scarce resources require new analytical methods to quantify fine-grained heterogeneity in malaria risk. Using routine national surveillance data from Swaziland (a sub-Saharan country on the verge of elimination), we estimated individual reproductive numbers. Fine-grained maps of reproductive numbers and local malaria importation rates were combined to show 'malariogenic potential', a first for malaria elimination. As countries approach elimination, these individual-based measures of transmission risk provide meaningful metrics for planning programmatic responses and prioritizing areas where interventions will contribute most to malaria elimination.

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

    PubMed

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

    2016-02-01

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

  8. Plasmodium falciparum phosphoethanolamine methyltransferase is essential for malaria transmission

    PubMed Central

    Bobenchik, April M.; Witola, William H.; Augagneur, Yoann; Nic Lochlainn, Laura; Garg, Aprajita; Pachikara, Niseema; Choi, Jae-Yeon; Zhao, Yang O.; Usmani-Brown, Sahar; Lee, Albert; Adjalley, Sophie H.; Samanta, Swapna; Fidock, David A.; Voelker, Dennis R.; Fikrig, Erol; Ben Mamoun, Choukri

    2013-01-01

    Efficient transmission of Plasmodium species between humans and Anopheles mosquitoes is a major contributor to the global burden of malaria. Gametocytogenesis, the process by which parasites switch from asexual replication within human erythrocytes to produce male and female gametocytes, is a critical step in malaria transmission and Plasmodium genetic diversity. Nothing is known about the pathways that regulate gametocytogenesis and only few of the current drugs that inhibit asexual replication are also capable of inhibiting gametocyte development and blocking malaria transmission. Here we provide genetic and pharmacological evidence indicating that the pathway for synthesis of phosphatidylcholine in Plasmodium falciparum membranes from host serine is essential for parasite gametocytogenesis and malaria transmission. Parasites lacking the phosphoethanolamine N-methyltransferase enzyme, which catalyzes the limiting step in this pathway, are severely altered in gametocyte development, are incapable of producing mature-stage gametocytes, and are not transmitted to mosquitoes. Chemical screening identified 11 inhibitors of phosphoethanolamine N-methyltransferase that block parasite intraerythrocytic asexual replication and gametocyte differentiation in the low micromolar range. Kinetic studies in vitro as well as functional complementation assays and lipid metabolic analyses in vivo on the most promising inhibitor NSC-158011 further demonstrated the specificity of inhibition. These studies set the stage for further optimization of NSC-158011 for development of a class of dual activity antimalarials to block both intraerythrocytic asexual replication and gametocytogenesis. PMID:24145416

  9. Malaria transmission modelling: a network perspective.

    PubMed

    Liu, Jiming; Yang, Bo; Cheung, William K; Yang, Guojing

    2012-11-01

    Malaria transmission can be affected by multiple or even hidden factors, making it difficult to timely and accurately predict the impact of elimination and eradication programs that have been undertaken and the potential resurgence and spread that may continue to emerge. One approach at the moment is to develop and deploy surveillance systems in an attempt to identify them as timely as possible and thus to enable policy makers to modify and implement strategies for further preventing the transmission. Most of the surveillance data will be of temporal and spatial nature. From an interdisciplinary point of view, it would be interesting to ask the following important as well as challenging question: Based on the available surveillance data in temporal and spatial forms, how can we build a more effective surveillance mechanism for monitoring and early detecting the relative prevalence and transmission patterns of malaria? What we can note from the existing clustering-based surveillance software systems is that they do not infer the underlying transmission networks of malaria. However, such networks can be quite informative and insightful as they characterize how malaria transmits from one place to another. They can also in turn allow public health policy makers and researchers to uncover the hidden and interacting factors such as environment, genetics and ecology and to discover/predict malaria transmission patterns/trends. The network perspective further extends the present approaches to modelling malaria transmission based on a set of chosen factors. In this article, we survey the related work on transmission network inference, discuss how such an approach can be utilized in developing an effective computational means for inferring malaria transmission networks based on partial surveillance data, and what methodological steps and issues may be involved in its formulation and validation.

  10. Socio-Demographics and the Development of Malaria Elimination Strategies in the Low Transmission Setting

    PubMed Central

    Chuquiyauri, Raul; Paredes, Maribel; Peñataro, Pablo; Torres, Sonia; Marin, Silvia; Tenorio, Alexander; Brouwer, Kimberly C.; Abeles, Shira; Llanos-Cuentas, Alejandro; Gilman, Robert H.; Kosek, Margaret; Vinetz, Joseph M.

    2011-01-01

    This analysis presents a comprehensive description of malaria burden and risk factors in Peruvian Amazon villages where malaria transmission is hypoendemic. More than 9,000 subjects were studied in contrasting village settings within the Department of Loreto, Peru, where most malaria occurs in the country. Plasmodium vivax is responsible for more than 75% of malaria cases; severe disease from any form of malaria is uncommon and death rare. The association between lifetime malaria episodes and individual and household covariates was studied using polychotomous logistic regression analysis, assessing effects on odds of some vs. no lifetime malaria episodes. Malaria morbidity during lifetime was strongly associated with age, logging, farming, travel history, and living with a logger or agriculturist. Select groups of adults, particularly loggers and agriculturists acquire multiple malaria infections in transmission settings outside of the main domicile, and may be mobile human reservoirs by which malaria parasites move within and between micro-regions within malaria endemic settings. For example, such individuals might well be reservoirs of transmission by introducing or reintroducing malaria into their home villages and their own households, depending on vector ecology and the local village setting. Therefore, socio-demographic studies can identify people with the epidemiological characteristic of transmission risk, and these individuals would be prime targets against which to deploy transmission blocking strategies along with insecticide treated bednets and chemoprophylaxis. PMID:22100446

  11. Targeting Human Transmission Biology for Malaria Elimination

    PubMed Central

    Buckee, Caroline; Marti, Matthias

    2015-01-01

    Malaria remains one of the leading causes of death worldwide, despite decades of public health efforts. The recent commitment by many endemic countries to eliminate malaria marks a shift away from programs aimed at controlling disease burden towards one that emphasizes reducing transmission of the most virulent human malaria parasite, Plasmodium falciparum. Gametocytes, the only developmental stage of malaria parasites able to infect mosquitoes, have remained understudied, as they occur in low numbers, do not cause disease, and are difficult to detect in vivo by conventional methods. Here, we review the transmission biology of P. falciparum gametocytes, featuring important recent discoveries of genes affecting parasite commitment to gametocyte formation, microvesicles enabling parasites to communicate with each other, and the anatomical site where immature gametocytes develop. We propose potential parasite targets for future intervention and highlight remaining knowledge gaps. PMID:26086192

  12. Modeling Malaria Transmission in Thailand and Indonesia

    NASA Technical Reports Server (NTRS)

    Kiang, Richard; Adimi, Farida; Nigro, Joseph

    2007-01-01

    Malaria Modeling and Surveillance is a project in the NASA Applied Sciences Public Health Applications Program. The main objectives of this project are: 1) identification of the potential breeding sites for major vector species: 2) implementation of a malaria transmission model to identify they key factors that sustain or intensify malaria transmission; and 3) implementation of a risk algorithm to predict the occurrence of malaria and its transmission intensity. Remote sensing and GIs are the essential elements of this project. The NASA Earth science data sets used in this project include AVHRR Pathfinder, TRMM, MODIS, NSIPP and SIESIP. Textural-contextual classifications are used to identify small larval habitats. Neural network methods are used to model malaria cases as a function of precipitation, temperatures, humidity and vegetation. Hindcastings based on these environmental parameters have shown good agreement to epidemiological records. Examples for spatio-temporal modeling of malaria transmissions in Southeast Asia are given. Discrete event simulations were used for modeling the detailed interactions among the vector life cycle, sporogonic cycle and human infection cycle, under the explicit influences of selected extrinsic and intrinsic factors. The output of the model includes the individual infection status and the quantities normally observed in field studies, such as mosquito biting rates, sporozoite infection rates, gametocyte prevalence and incidence. Results are in good agreement with mosquito vector and human malaria data acquired by Coleman et al. over 4.5 years in Kong Mong Tha, a remote village in western Thailand. Application of our models is not restricted to Southeast Asia. The model and techniques are equally applicable to other regions of the world, when appropriate epidemiological and vector ecological parameters are used as input.

  13. Modelling climate change and malaria transmission.

    PubMed

    Parham, Paul E; Michael, Edwin

    2010-01-01

    The impact of climate change on human health has received increasing attention in recent years, with potential impacts due to vector-borne diseases only now beginning to be understood. As the most severe vector-borne disease, with one million deaths globally in 2006, malaria is thought most likely to be affected by changes in climate variables due to the sensitivity of its transmission dynamics to environmental conditions. While considerable research has been carried out using statistical models to better assess the relationship between changes in environmental variables and malaria incidence, less progress has been made on developing process-based climate-driven mathematical models with greater explanatory power. Here, we develop a simple model of malaria transmission linked to climate which permits useful insights into the sensitivity of disease transmission to changes in rainfall and temperature variables. Both the impact of changes in the mean values of these key external variables and importantly temporal variation in these values are explored. We show that the development and analysis of such dynamic climate-driven transmission models will be crucial to understanding the rate at which P. falciparum and P. vivax may either infect, expand into or go extinct in populations as local environmental conditions change. Malaria becomes endemic in a population when the basic reproduction number R0 is greater than unity and we identify an optimum climate-driven transmission window for the disease, thus providing a useful indicator for determing how transmission risk may change as climate changes. Overall, our results indicate that considerable work is required to better understand ways in which global malaria incidence and distribution may alter with climate change. In particular, we show that the roles of seasonality, stochasticity and variability in environmental variables, as well as ultimately anthropogenic effects, require further study. The work presented here

  14. Measuring malaria endemicity from intense to interrupted transmission

    PubMed Central

    Hay, Simon I; Smith, David L; Snow, Robert W

    2008-01-01

    Summary The quantification of malaria transmission for the classification of malaria risk has long been a concern for epidemiologists. During the era of the Global Malaria Eradication Programme, measurements of malaria endemicity were institutionalised by their incorporation into rules outlining defined action points for malaria control programmes. We review the historical development of these indices and their contemporary relevance. This is at a time when many malaria-endemic countries are scaling-up their malaria control activities and reconsidering their prospects for elimination. These considerations are also important to an international community that has recently been challenged to revaluate the prospects for malaria eradication. PMID:18387849

  15. Quantifying Transmission Investment in Malaria Parasites.

    PubMed

    Greischar, Megan A; Mideo, Nicole; Read, Andrew F; Bjørnstad, Ottar N

    2016-02-01

    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.

  16. Quantifying Transmission Investment in Malaria Parasites

    PubMed Central

    Greischar, Megan A.; Mideo, Nicole; Read, Andrew F.; Bjørnstad, Ottar N.

    2016-01-01

    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. PMID:26890485

  17. Larvivorous fish for preventing malaria transmission

    PubMed Central

    Walshe, Deirdre P; Garner, Paul; Abdel-Hameed Adeel, Ahmed A; Pyke, Graham H; Burkot, Tom

    2013-01-01

    Background Adult anopheline mosquitoes transmit Plasmodium parasites that cause malaria. Some fish species eat mosquito larvae and pupae. In disease control policy documents, the World Health Organization includes biological control of malaria vectors by stocking ponds, rivers, and water collections near where people live with larvivorous fish to reduce Plasmodium parasite transmission. The Global Fund finances larvivorous fish programmes in some countries, and, with increasing efforts in eradication of malaria, policy makers may return to this option. We therefore assessed the evidence base for larvivorous fish programmes in malaria control. Objectives Our main objective was to evaluate whether introducing larvivorous fish to anopheline breeding sites impacts Plasmodium parasite transmission. Our secondary objective was to summarize studies evaluating whether introducing larvivorous fish influences the density and presence of Anopheles larvae and pupae in water sources, to understand whether fish can possibly have an effect. Search methods We attempted to identify all relevant studies regardless of language or publication status (published, unpublished, in press, or ongoing). We searched the following databases: the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library; MEDLINE; EMBASE; CABS Abstracts; LILACS; and the metaRegister of Controlled Trials (mRCT) until 18 June 2013. We checked the reference lists of all studies identified by the above methods. We also examined references listed in review articles and previously compiled bibliographies to look for eligible studies. Selection criteria Randomized controlled trials and non-randomized controlled trials, including controlled before-and-after studies, controlled time series and controlled interrupted time series studies from malaria-endemic regions that introduced fish as a larvicide and reported on malaria in

  18. Prevalence of Plasmodium falciparum transmission reducing immunity among primary school children in a malaria moderate transmission region in Zimbabwe.

    PubMed

    Paul, Noah H; Vengesai, Arthur; Mduluza, Takafira; Chipeta, James; Midzi, Nicholas; Bansal, Geetha P; Kumar, Nirbhay

    2016-11-01

    transmission reducing immunity in school age children from a moderate transmission area of malaria, and provide further support to exploit target antigens such as Pfs48/45 for further development of a malaria transmission blocking vaccine.

  19. Defining the Global Spatial Limits of Malaria Transmission in 2005

    PubMed Central

    Guerra, C.A.; Snow, R.W.; Hay, S.I.

    2011-01-01

    There is no accurate contemporary global map of the distribution of malaria. We show how guidelines formulated to advise travellers on appropriate chemoprophylaxis for areas of reported Plasmodium falciparum and Plasmodium vivax malaria risk can be used to generate crude spatial limits. We first review and amalgamate information on these guidelines to define malaria risk at national and sub-national administrative boundary levels globally. We then adopt an iterative approach to reduce these extents by applying a series of biological limits imposed by altitude, climate and population density to malaria transmission, specific to the local dominant vector species. Global areas of, and population at risk from, P. falciparum and often-neglected P. vivax malaria are presented for 2005 for all malaria endemic countries. These results reveal that more than 3 billion people were at risk of malaria in 2005. PMID:16647970

  20. Early warnings of the potential for malaria transmission in Rural Africa using the Hydrology, Entomology and Malaria Transmission Simulator (HYDREMATS)

    NASA Astrophysics Data System (ADS)

    Yamana, T. K.; Eltahir, E. A.

    2010-12-01

    Early warnings of malaria transmission allow health officials to better prepare for future epidemics. Monitoring rainfall is recognized as an important part of malaria early warning systems, as outlined by the Roll Back Malaria Initiative. The Hydrology, Entomology and Malaria Simulator (HYDREMATS) is a mechanistic model that relates rainfall to malaria transmission, and could be used to provide early warnings of malaria epidemics. HYDREMATS is used to make predictions of mosquito populations and vectorial capacity for 2005, 2006, and 2007 in Banizoumbou village in western Niger. HYDREMATS is forced by observed rainfall, followed by a rainfall prediction based on the seasonal mean rainfall for a period two or four weeks into the future. Predictions made using this method provided reasonable estimates of mosquito populations and vectorial capacity, two to four weeks in advance. The predictions were significantly improved compared to those made when HYDREMATS was forced with seasonal mean rainfall alone.

  1. Identifying Malaria Transmission Foci for Elimination Using Human Mobility Data.

    PubMed

    Ruktanonchai, Nick W; DeLeenheer, Patrick; Tatem, Andrew J; Alegana, Victor A; Caughlin, T Trevor; Zu Erbach-Schoenberg, Elisabeth; Lourenço, Christopher; Ruktanonchai, Corrine W; Smith, David L

    2016-04-01

    Humans move frequently and tend to carry parasites among areas with endemic malaria and into areas where local transmission is unsustainable. Human-mediated parasite mobility can thus sustain parasite populations in areas where they would otherwise be absent. Data describing human mobility and malaria epidemiology can help classify landscapes into parasite demographic sources and sinks, ecological concepts that have parallels in malaria control discussions of transmission foci. By linking transmission to parasite flow, it is possible to stratify landscapes for malaria control and elimination, as sources are disproportionately important to the regional persistence of malaria parasites. Here, we identify putative malaria sources and sinks for pre-elimination Namibia using malaria parasite rate (PR) maps and call data records from mobile phones, using a steady-state analysis of a malaria transmission model to infer where infections most likely occurred. We also examined how the landscape of transmission and burden changed from the pre-elimination setting by comparing the location and extent of predicted pre-elimination transmission foci with modeled incidence for 2009. This comparison suggests that while transmission was spatially focal pre-elimination, the spatial distribution of cases changed as burden declined. The changing spatial distribution of burden could be due to importation, with cases focused around importation hotspots, or due to heterogeneous application of elimination effort. While this framework is an important step towards understanding progressive changes in malaria distribution and the role of subnational transmission dynamics in a policy-relevant way, future work should account for international parasite movement, utilize real time surveillance data, and relax the steady state assumption required by the presented model.

  2. Identifying Malaria Transmission Foci for Elimination Using Human Mobility Data

    PubMed Central

    Ruktanonchai, Nick W.; DeLeenheer, Patrick; Tatem, Andrew J.; Alegana, Victor A.; Caughlin, T. Trevor; zu Erbach-Schoenberg, Elisabeth; Lourenço, Christopher; Ruktanonchai, Corrine W.; Smith, David L.

    2016-01-01

    Humans move frequently and tend to carry parasites among areas with endemic malaria and into areas where local transmission is unsustainable. Human-mediated parasite mobility can thus sustain parasite populations in areas where they would otherwise be absent. Data describing human mobility and malaria epidemiology can help classify landscapes into parasite demographic sources and sinks, ecological concepts that have parallels in malaria control discussions of transmission foci. By linking transmission to parasite flow, it is possible to stratify landscapes for malaria control and elimination, as sources are disproportionately important to the regional persistence of malaria parasites. Here, we identify putative malaria sources and sinks for pre-elimination Namibia using malaria parasite rate (PR) maps and call data records from mobile phones, using a steady-state analysis of a malaria transmission model to infer where infections most likely occurred. We also examined how the landscape of transmission and burden changed from the pre-elimination setting by comparing the location and extent of predicted pre-elimination transmission foci with modeled incidence for 2009. This comparison suggests that while transmission was spatially focal pre-elimination, the spatial distribution of cases changed as burden declined. The changing spatial distribution of burden could be due to importation, with cases focused around importation hotspots, or due to heterogeneous application of elimination effort. While this framework is an important step towards understanding progressive changes in malaria distribution and the role of subnational transmission dynamics in a policy-relevant way, future work should account for international parasite movement, utilize real time surveillance data, and relax the steady state assumption required by the presented model. PMID:27043913

  3. A review of malaria transmission dynamics in forest ecosystems

    PubMed Central

    2014-01-01

    Malaria continues to be a major health problem in more than 100 endemic countries located primarily in tropical and sub-tropical regions around the world. Malaria transmission is a dynamic process and involves many interlinked factors, from uncontrollable natural environmental conditions to man-made disturbances to nature. Almost half of the population at risk of malaria lives in forest areas. Forests are hot beds of malaria transmission as they provide conditions such as vegetation cover, temperature, rainfall and humidity conditions that are conducive to distribution and survival of malaria vectors. Forests often lack infrastructure and harbor tribes with distinct genetic traits, socio-cultural beliefs and practices that greatly influence malaria transmission dynamics. Here we summarize the various topographical, entomological, parasitological, human ecological and socio-economic factors, which are crucial and shape malaria transmission in forested areas. An in-depth understanding and synthesis of the intricate relationship of these parameters in achieving better malaria control in various types of forest ecosystems is emphasized. PMID:24912923

  4. Optimal temperature for malaria transmission is dramaticallylower than previously predicted

    USGS Publications Warehouse

    Mordecai, Eerin A.; Paaijmans, Krijin P.; Johnson, Leah R.; Balzer, Christian; Ben-Horin, Tal; de Moor, Emily; McNally, Amy; Pawar, Samraat; Ryan, Sadie J.; Smith, Thomas C.; Lafferty, Kevin D.

    2013-01-01

    The ecology of mosquito vectors and malaria parasites affect the incidence, seasonal transmission and geographical range of malaria. Most malaria models to date assume constant or linear responses of mosquito and parasite life-history traits to temperature, predicting optimal transmission at 31 °C. These models are at odds with field observations of transmission dating back nearly a century. We build a model with more realistic ecological assumptions about the thermal physiology of insects. Our model, which includes empirically derived nonlinear thermal responses, predicts optimal malaria transmission at 25 °C (6 °C lower than previous models). Moreover, the model predicts that transmission decreases dramatically at temperatures > 28 °C, altering predictions about how climate change will affect malaria. A large data set on malaria transmission risk in Africa validates both the 25 °C optimum and the decline above 28 °C. Using these more accurate nonlinear thermal-response models will aid in understanding the effects of current and future temperature regimes on disease transmission.

  5. Costs of crowding for the transmission of malaria parasites

    PubMed Central

    Pollitt, Laura C; Churcher, Thomas S; Dawes, Emma J; Khan, Shahid M; Sajid, Mohammed; Basáñez, María-Gloria; Colegrave, Nick; Reece, Sarah E

    2013-01-01

    The utility of using evolutionary and ecological frameworks to understand the dynamics of infectious diseases is gaining increasing recognition. However, integrating evolutionary ecology and infectious disease epidemiology is challenging because within-host dynamics can have counterintuitive consequences for between-host transmission, especially for vector-borne parasites. A major obstacle to linking within- and between-host processes is that the drivers of the relationships between the density, virulence, and fitness of parasites are poorly understood. By experimentally manipulating the intensity of rodent malaria (Plasmodium berghei) infections in Anopheles stephensi mosquitoes under different environmental conditions, we show that parasites experience substantial density-dependent fitness costs because crowding reduces both parasite proliferation and vector survival. We then use our data to predict how interactions between parasite density and vector environmental conditions shape within-vector processes and onward disease transmission. Our model predicts that density-dependent processes can have substantial and unexpected effects on the transmission potential of vector-borne disease, which should be considered in the development and evaluation of transmission-blocking interventions. PMID:23789029

  6. Chemotherapeutic strategies for reducing transmission of Plasmodium vivax malaria.

    PubMed

    Douglas, Nicholas M; John, George K; von Seidlein, Lorenz; Anstey, Nicholas M; Price, Ric N

    2012-01-01

    Effective use of anti-malarial drugs is key to reducing the transmission potential of Plasmodium vivax. In patients presenting with symptomatic disease, treatment with potent and relatively slowly eliminated blood schizontocidal regimens administered concurrently with a supervised course of 7 mg/kg primaquine over 7-14 days has potential to exert the greatest transmission-blocking benefit. Given the spread of chloroquine-resistant P. vivax strains, the artemisinin combination therapies dihydroartemisinin + piperaquine and artesunate + mefloquine are currently the most assured means of preventing P. vivax recrudescence. Preliminary evidence suggests that, like chloroquine, these combinations potentiate the hypnozoitocidal effect of primaquine, but further supportive evidence is required. In view of the high rate of P. vivax relapse following falciparum infections in co-endemic regions, there is a strong argument for broadening current radical cure policy to include the administration of hypnozoitocidal doses of primaquine to patients with Plasmodium falciparum malaria. The most important reservoir for P. vivax transmission is likely to be very low-density, asymptomatic infections, the majority of which will arise from liver-stage relapses. Therefore, judicious mass administration of hypnozoitocidal therapy will reduce transmission of P. vivax to a greater extent than strategies focused on treatment of symptomatic patients. An efficacious hypnozoitocidal agent with a short curative treatment course would be particularly useful in mass drug administration campaigns.

  7. Multifocal autochthonous transmission of malaria--Florida, 2003.

    PubMed

    2004-05-21

    The majority of malaria cases diagnosed in the United States are imported, usually by persons traveling from areas where malaria is endemic. However, small outbreaks of locally acquired mosquito-borne malaria continue to occur. During July-September 2003, an outbreak of malaria (eight cases of Plasmodium vivax malaria) occurred in Palm Beach County, Florida. During the same period, two patients were evaluated for malaria in neighboring Okeechobee County, approximately 75 miles from the Palm Beach County transmission area. One patient was thought to have acquired infection with the same parasite species (P. vivax), and concerns were raised about a possible link. To determine whether infection was acquired in Okeechobee County and whether a possible link existed to the Palm Beach County outbreak, the Florida Department of Health (FDOH) initiated an investigation. This report describes that investigation, which determined that although initial laboratory results suggested local transmission, subsequent evaluation and testing confirmed the case as imported malaria. These findings underscore the importance of a rapid and thorough investigation of any malaria case suspected to be acquired through local mosquito-borne transmission.

  8. Urbanization, malaria transmission and disease burden in Africa

    PubMed Central

    Hay, Simon I.; Guerra, Carlos A.; Tatem, Andrew J.; Atkinson, Peter M.; Snow, Robert W.

    2011-01-01

    Many attempts have been made to quantify Africa’s malaria burden but none has addressed how urbanization will affect disease transmission and outcome, and therefore mortality and morbidity estimates. In 2003, 39% of Africa’s 850 million people lived in urban settings; by 2030, 54% of Africans are expected to do so. We present the results of a series of entomological, parasitological and behavioural meta-analyses of studies that have investigated the effect of urbanization on malaria in Africa. We describe the effect of urbanization on both the impact of malaria transmission and the concomitant improvements in access to preventative and curative measures. Using these data, we have recalculated estimates of populations at risk of malaria and the resulting mortality. We find there were 1,068,505 malaria deaths in Africa in 2000 — a modest 6.7% reduction over previous iterations. The public-health implications of these findings and revised estimates are discussed. PMID:15608702

  9. Antibodies to plant-produced Plasmodium falciparum sexual stage protein Pfs25 exhibit transmission blocking activity.

    PubMed

    Farrance, Christine E; Chichester, Jessica A; Musiychuk, Konstantin; Shamloul, Moneim; Rhee, Amy; Manceva, Slobodanka D; Jones, R Mark; Mamedov, Tarlan; Sharma, Satish; Mett, Vadim; Streatfield, Stephen J; Roeffen, Will; van de Vegte-Bolmer, Marga; Sauerwein, Robert W; Wu, Yimin; Muratova, Olga; Miller, Louis; Duffy, Patrick; Sinden, Robert; Yusibov, Vidadi

    2011-01-01

    Malaria is a serious and sometimes fatal mosquito-borne disease caused by a protozoan parasite. Each year, it is estimated that over one million people are killed by malaria, yet the disease is preventable and treatable. Developing vaccines against the parasite is a critical component in the fight against malaria and these vaccines can target different stages of the pathogen's life cycle. We are targeting sexual stage proteins of P. falciparum which are found on the surface of the parasite reproductive cells present in the mosquito gut. Antibodies against these proteins block the progression of the parasite's life cycle in the mosquito, and thus block transmission to the next human host. Transmission blocking vaccines are essential to the malaria eradication program to ease the disease burden at the population level. We have successfully produced multiple versions of the Pfs25 antigen in a plant virus-based transient expression system and have evaluated these vaccine candidates in an animal model. The targets are expressed in plants at a high level, are soluble and most importantly, generate strong transmission blocking activity as determined by a standard membrane feeding assay. These data demonstrate the feasibility of expressing Plasmodium antigens in a plant-based system for the economic production of a transmission blocking vaccine against malaria.

  10. Agent-Based Simulations of Malaria Transmissions with Applications to a Study Site in Thailand

    NASA Technical Reports Server (NTRS)

    Kiang, Richard K.; Adimi, Farida; Zollner, Gabriela E.; Coleman, Russell E.

    2006-01-01

    The dynamics of malaria transmission are driven by environmental, biotic and socioeconomic factors. Because of the geographic dependency of these factors and the complex interactions among them, it is difficult to generalize the key factors that perpetuate or intensify malaria transmission. Methods: Discrete event simulations were used for modeling the detailed interactions among the vector life cycle, sporogonic cycle and human infection cycle, under the explicit influences of selected extrinsic and intrinsic factors. Meteorological and environmental parameters may be derived from satellite data. The output of the model includes the individual infection status and the quantities normally observed in field studies, such as mosquito biting rates, sporozoite infection rates, gametocyte prevalence and incidence. Results were compared with mosquito vector and human malaria data acquired over 4.5 years (June 1999 - January 2004) in Kong Mong Tha, a remote village in Kanchanaburi Province, western Thailand. Results: Three years of transmissions of vivax and falciparum malaria were simulated for a hypothetical hamlet with approximately 1/7 of the study site population. The model generated results for a number of scenarios, including applications of larvicide and insecticide, asymptomatic cases receiving or not receiving treatment, blocking malaria transmission in mosquito vectors, and increasing the density of farm (host) animals in the hamlet. Transmission characteristics and trends in the simulated results are comparable to actual data collected at the study site.

  11. Estimating malaria transmission from humans to mosquitoes in a noisy landscape.

    PubMed

    Reiner, Robert C; Guerra, Carlos; Donnelly, Martin J; Bousema, Teun; Drakeley, Chris; Smith, David L

    2015-10-06

    A basic quantitative understanding of malaria transmission requires measuring the probability a mosquito becomes infected after feeding on a human. Parasite prevalence in mosquitoes is highly age-dependent, and the unknown age-structure of fluctuating mosquito populations impedes estimation. Here, we simulate mosquito infection dynamics, where mosquito recruitment is modelled seasonally with fractional Brownian noise, and we develop methods for estimating mosquito infection rates. We find that noise introduces bias, but the magnitude of the bias depends on the 'colour' of the noise. Some of these problems can be overcome by increasing the sampling frequency, but estimates of transmission rates (and estimated reductions in transmission) are most accurate and precise if they combine parity, oocyst rates and sporozoite rates. These studies provide a basis for evaluating the adequacy of various entomological sampling procedures for measuring malaria parasite transmission from humans to mosquitoes and for evaluating the direct transmission-blocking effects of a vaccine.

  12. Estimating malaria transmission from humans to mosquitoes in a noisy landscape

    PubMed Central

    Reiner, Robert C.; Guerra, Carlos; Donnelly, Martin J.; Bousema, Teun; Drakeley, Chris; Smith, David L.

    2015-01-01

    A basic quantitative understanding of malaria transmission requires measuring the probability a mosquito becomes infected after feeding on a human. Parasite prevalence in mosquitoes is highly age-dependent, and the unknown age-structure of fluctuating mosquito populations impedes estimation. Here, we simulate mosquito infection dynamics, where mosquito recruitment is modelled seasonally with fractional Brownian noise, and we develop methods for estimating mosquito infection rates. We find that noise introduces bias, but the magnitude of the bias depends on the ‘colour' of the noise. Some of these problems can be overcome by increasing the sampling frequency, but estimates of transmission rates (and estimated reductions in transmission) are most accurate and precise if they combine parity, oocyst rates and sporozoite rates. These studies provide a basis for evaluating the adequacy of various entomological sampling procedures for measuring malaria parasite transmission from humans to mosquitoes and for evaluating the direct transmission-blocking effects of a vaccine. PMID:26400195

  13. Clinical algorithm for malaria during low and high transmission seasons

    PubMed Central

    Muhe, L.; Oljira, B.; Degefu, H.; Enquesellassie, F.; Weber, M.

    1999-01-01

    OBJECTIVES—To assess the proportion of children with febrile disease who suffer from malaria and to identify clinical signs and symptoms that predict malaria during low and high transmission seasons.
STUDY DESIGN—2490 children aged 2 to 59 months presenting to a health centre in rural Ethiopia with fever had their history documented and the following investigations: clinical examination, diagnosis, haemoglobin measurement, and a blood smear for malaria parasites. Clinical findings were related to the presence of malaria parasitaemia.
RESULTS—Malaria contributed to 5.9% of all febrile cases from January to April and to 30.3% during the rest of the year. Prediction of malaria was improved by simple combinations of a few signs and symptoms. Fever with a history of previous malarial attack or absence of cough or a finding of pallor gave a sensitivity of 83% in the high risk season and 75% in the low risk season, with corresponding specificities of 51% and 60%; fever with a previous malaria attack or pallor or splenomegaly had sensitivities of 80% and 69% and specificities of 65% and 81% in high and low risk settings, respectively.
CONCLUSION—Better clinical definitions are possible for low malaria settings when microscopic examination cannot be done. Health workers should be trained to detect pallor and splenomegaly because these two signs improve the specificity for malaria.

 PMID:10451393

  14. A climate distribution model of malaria transmission in Sudan.

    PubMed

    Musa, Mohammed I; Shohaimi, Shamarina; Hashim, Nor R; Krishnarajah, Isthrinayagy

    2012-11-01

    Malaria remains a major health problem in Sudan. With a population exceeding 39 million, there are around 7.5 million cases and 35,000 deaths every year. The predicted distribution of malaria derived from climate factors such as maximum and minimum temperatures, rainfall and relative humidity was compared with the actual number of malaria cases in Sudan for the period 2004 to 2010. The predictive calculations were done by fuzzy logic suitability (FLS) applied to the numerical distribution of malaria transmission based on the life cycle characteristics of the Anopheles mosquito accounting for the impact of climate factors on malaria transmission. This information is visualized as a series of maps (presented in video format) using a geographical information systems (GIS) approach. The climate factors were found to be suitable for malaria transmission in the period of May to October, whereas the actual case rates of malaria were high from June to November indicating a positive correlation. While comparisons between the prediction model for June and the case rate model for July did not show a high degree of association (18%), the results later in the year were better, reaching the highest level (55%) for October prediction and November case rate.

  15. Strategies & recent development of transmission-blocking vaccines against Plasmodium falciparum

    PubMed Central

    Chaturvedi, Neha; Bharti, Praveen K.; Tiwari, Archana; Singh, Neeru

    2016-01-01

    Transmission blocking malaria vaccines are aimed to block the development and maturity of sexual stages of parasite within mosquitoes. The vaccine candidate antigens (Pfs25, Pfs48/45, Pfs230) that have shown transmission blocking immunity in model systems are in different stages of development. These antigens are immunogenic with limited genetic diversity. Pfs25 is a leading candidate and currently in phase I clinical trial. Efforts are now focused on the cost-effective production of potent antigens using safe adjuvants and optimization of vaccine delivery system that are capable of inducing strong immune responses. This review addresses the potential usefulness, development strategies, challenges, clinical trials and current status of Plasmodium falciparum sexual stage malaria vaccine candidate antigens for the development of transmission-blocking vaccines. PMID:27748294

  16. Malaria transmission potential could be reduced with current and future climate change

    PubMed Central

    Murdock, C. C.; Sternberg, E. D.; Thomas, M. B.

    2016-01-01

    Several studies suggest the potential for climate change to increase malaria incidence in cooler, marginal transmission environments. However, the effect of increasing temperature in warmer regions where conditions currently support endemic transmission has received less attention. We investigate how increases in temperature from optimal conditions (27 °C to 30 °C and 33 °C) interact with realistic diurnal temperature ranges (DTR: ± 0 °C, 3 °C, and 4.5 °C) to affect the ability of key vector species from Africa and Asia (Anopheles gambiae and An. stephensi) to transmit the human malaria parasite, Plasmodium falciparum. The effects of increasing temperature and DTR on parasite prevalence, parasite intensity, and mosquito mortality decreased overall vectorial capacity for both mosquito species. Increases of 3 °C from 27 °C reduced vectorial capacity by 51–89% depending on species and DTR, with increases in DTR alone potentially halving transmission. At 33 °C, transmission potential was further reduced for An. stephensi and blocked completely in An. gambiae. These results suggest that small shifts in temperature could play a substantial role in malaria transmission dynamics, yet few empirical or modeling studies consider such effects. They further suggest that rather than increase risk, current and future warming could reduce transmission potential in existing high transmission settings. PMID:27324146

  17. Malaria transmission potential could be reduced with current and future climate change.

    PubMed

    Murdock, C C; Sternberg, E D; Thomas, M B

    2016-06-21

    Several studies suggest the potential for climate change to increase malaria incidence in cooler, marginal transmission environments. However, the effect of increasing temperature in warmer regions where conditions currently support endemic transmission has received less attention. We investigate how increases in temperature from optimal conditions (27 °C to 30 °C and 33 °C) interact with realistic diurnal temperature ranges (DTR: ± 0 °C, 3 °C, and 4.5 °C) to affect the ability of key vector species from Africa and Asia (Anopheles gambiae and An. stephensi) to transmit the human malaria parasite, Plasmodium falciparum. The effects of increasing temperature and DTR on parasite prevalence, parasite intensity, and mosquito mortality decreased overall vectorial capacity for both mosquito species. Increases of 3 °C from 27 °C reduced vectorial capacity by 51-89% depending on species and DTR, with increases in DTR alone potentially halving transmission. At 33 °C, transmission potential was further reduced for An. stephensi and blocked completely in An. gambiae. These results suggest that small shifts in temperature could play a substantial role in malaria transmission dynamics, yet few empirical or modeling studies consider such effects. They further suggest that rather than increase risk, current and future warming could reduce transmission potential in existing high transmission settings.

  18. High-Throughput Assay and Discovery of Small Molecules that Interrupt Malaria Transmission

    PubMed Central

    Plouffe, David M.; Wree, Melanie; Du, Alan Y.; Meister, Stephan; Li, Fengwu; Patra, Kailash; Lubar, Aristea; Okitsu, Shinji L.; Flannery, Erika L.; Kato, Nobutaka; Tanaseichuk, Olga; Comer, Eamon; Zhou, Bin; Kuhen, Kelli; Zhou, Yingyao; Leroy, Didier; Schreiber, Stuart L.; Scherer, Christina A.; Vinetz, Joseph; Winzeler, Elizabeth A.

    2016-01-01

    Summary Preventing transmission is an important element of malaria control. However, most of the current available methods to assay for malaria transmission blocking are relatively low throughput and cannot be applied to large chemical libraries. We have developed a high-throughput and cost-effective assay, the Saponin-lysis Sexual Stage Assay (SaLSSA), for identifying small molecules with transmission-blocking capacity. SaLSSA analysis of 13,983 unique compounds uncovered that >90% of well-characterized antimalarials, including endoperoxides and 4-aminoquinolines, as well as compounds active against asexual blood stages, lost most of their killing activity when parasites developed into metabolically quiescent stage V gametocytes. On the other hand, we identified compounds with consistent low nanomolar transmission-blocking activity, some of which showed cross-reactivity against asexual blood and liver stages. The data clearly emphasize substantial physiological differences between sexual and asexual parasites and provide a tool and starting points for the discovery and development of transmission-blocking drugs. PMID:26749441

  19. High-Throughput Assay and Discovery of Small Molecules that Interrupt Malaria Transmission.

    PubMed

    Plouffe, David M; Wree, Melanie; Du, Alan Y; Meister, Stephan; Li, Fengwu; Patra, Kailash; Lubar, Aristea; Okitsu, Shinji L; Flannery, Erika L; Kato, Nobutaka; Tanaseichuk, Olga; Comer, Eamon; Zhou, Bin; Kuhen, Kelli; Zhou, Yingyao; Leroy, Didier; Schreiber, Stuart L; Scherer, Christina A; Vinetz, Joseph; Winzeler, Elizabeth A

    2016-01-13

    Preventing transmission is an important element of malaria control. However, most of the current available methods to assay for malaria transmission blocking are relatively low throughput and cannot be applied to large chemical libraries. We have developed a high-throughput and cost-effective assay, the Saponin-lysis Sexual Stage Assay (SaLSSA), for identifying small molecules with transmission-blocking capacity. SaLSSA analysis of 13,983 unique compounds uncovered that >90% of well-characterized antimalarials, including endoperoxides and 4-aminoquinolines, as well as compounds active against asexual blood stages, lost most of their killing activity when parasites developed into metabolically quiescent stage V gametocytes. On the other hand, we identified compounds with consistent low nanomolar transmission-blocking activity, some of which showed cross-reactivity against asexual blood and liver stages. The data clearly emphasize substantial physiological differences between sexual and asexual parasites and provide a tool and starting points for the discovery and development of transmission-blocking drugs.

  20. Modeling the risk of malaria for travelers to areas with stable malaria transmission

    PubMed Central

    2009-01-01

    Background Malaria is an important threat to travelers visiting endemic regions. The risk of acquiring malaria is complex and a number of factors including transmission intensity, duration of exposure, season of the year and use of chemoprophylaxis have to be taken into account estimating risk. Materials and methods A mathematical model was developed to estimate the risk of non-immune individual acquiring falciparum malaria when traveling to the Amazon region of Brazil. The risk of malaria infection to travelers was calculated as a function of duration of exposure and season of arrival. Results The results suggest significant variation of risk for non-immune travelers depending on arrival season, duration of the visit and transmission intensity. The calculated risk for visitors staying longer than 4 months during peak transmission was 0.5% per visit. Conclusions Risk estimates based on mathematical modeling based on accurate data can be a valuable tool in assessing risk/benefits and cost/benefits when deciding on the value of interventions for travelers to malaria endemic regions. PMID:20015392

  1. Blocking transmission of vector-borne diseases.

    PubMed

    Schorderet-Weber, Sandra; Noack, Sandra; Selzer, Paul M; Kaminsky, Ronald

    2017-04-01

    Vector-borne diseases are responsible for significant health problems in humans, as well as in companion and farm animals. Killing the vectors with ectoparasitic drugs before they have the opportunity to pass on their pathogens could be the ideal way to prevent vector borne diseases. Blocking of transmission might work when transmission is delayed during blood meal, as often happens in ticks. The recently described systemic isoxazolines have been shown to successfully prevent disease transmission under conditions of delayed pathogen transfer. However, if the pathogen is transmitted immediately at bite as it is the case with most insects, blocking transmission becomes only possible if ectoparasiticides prevent the vector from landing on or, at least, from biting the host. Chemical entities exhibiting repellent activity in addition to fast killing, like pyrethroids, could prevent pathogen transmission even in cases of immediate transfer. Successful blocking depends on effective action in the context of the extremely diverse life-cycles of vectors and vector-borne pathogens of medical and veterinary importance which are summarized in this review. This complexity leads to important parameters to consider for ectoparasiticide research and when considering the ideal drug profile for preventing disease transmission.

  2. Vulnerability to changes in malaria transmission due to climate change in West Africa

    NASA Astrophysics Data System (ADS)

    Yamana, T. K.; Eltahir, E. A.

    2012-12-01

    Malaria transmission in West Africa is strongly tied to climate; temperature affects the development rate of the malaria parasite, as well as the survival of the mosquitoes that transmit the disease, and rainfall is tied to mosquito abundance, as the vector lays its eggs in rain-fed water pools. As a result, the environmental suitability for malaria transmission in this region is expected to change as temperatures rise and rainfall patterns are altered. The vulnerability to changes in transmission varies throughout West Africa. Areas where malaria prevalence is already very high will be less sensitive to changes in transmission. Increases in environmental suitability for malaria transmission in the most arid regions may still be insufficient to allow sustained transmission. However, areas were malaria transmission currently occurs at low levels are expected to be the most sensitive to changes in environmental suitability for transmission. Here, we use data on current environment and malaria transmission rates to highlight areas in West Africa that we expect to be most vulnerable to an increase in malaria under certain climate conditions. We then analyze climate predictions from global climate models in vulnerable areas, and make predictions for the expected change in environmental suitability for malaria transmission using the Hydrology, Entomology and Malaria Transmission Simulator (HYDREMATS), a mechanistic model developed to simulate village-scale response of malaria transmission to environmental variables in West Africa.

  3. Rationale for the Coadministration of Albendazole and Ivermectin to Humans for Malaria Parasite Transmission Control

    DTIC Science & Technology

    2014-07-28

    STHs). Malaria and STHs overlap in distribution, and STH infections are associated with increased risk for malaria. Indeed, there is evidence that...suggests that STH infection may facilitate malaria transmission. Malaria and STH coinfection may exacerbate anemia, especially in pregnant women, leading...are a diverse group of infectious diseases including STH infections , lymphatic filariasis (LF), schistosomiasis, onchocerciasis, and at least 13

  4. Vector movement underlies avian malaria at upper elevation in Hawaii: implications for transmission of human malaria.

    PubMed

    Freed, Leonard A; Cann, Rebecca L

    2013-11-01

    With climate warming, malaria in humans and birds at upper elevations is an emerging infectious disease because development of the parasite in the mosquito vector and vector life history are both temperature dependent. An enhanced-mosquito-movement model from climate warming predicts increased transmission of malaria at upper elevation sites that are too cool for parasite development in the mosquito vector. We evaluate this model with avian malaria (Plasmodium relictum) at 1,900-m elevation on the Island of Hawaii, with air temperatures too low for sporogony in the vector (Culex quinquefasciatus). On a well-defined site over a 14-year period, 10 of 14 species of native and introduced birds became infected, several epizootics occurred, and the increase in prevalence was driven more by resident species than by mobile species that could have acquired their infections at lower elevations. Greater movement of infectious mosquitoes from lower elevations now permits avian malaria to spread at 1,900 m in Hawaii, in advance of climate warming at that elevation. The increase in malaria at upper elevations due to dispersal of infectious mosquitoes is a real alternative to temperature for the increased incidence of human malaria in tropical highlands.

  5. Malaria transmission, infection, and disease at three sites with varied transmission intensity in Uganda: implications for malaria control.

    PubMed

    Kamya, Moses R; Arinaitwe, Emmanuel; Wanzira, Humphrey; Katureebe, Agaba; Barusya, Chris; Kigozi, Simon P; Kilama, Maxwell; Tatem, Andrew J; Rosenthal, Philip J; Drakeley, Chris; Lindsay, Steve W; Staedke, Sarah G; Smith, David L; Greenhouse, Bryan; Dorsey, Grant

    2015-05-01

    The intensification of control interventions has led to marked reductions in malaria burden in some settings, but not others. To provide a comprehensive description of malaria epidemiology in Uganda, we conducted surveillance studies over 24 months in 100 houses randomly selected from each of three subcounties: Walukuba (peri-urban), Kihihi (rural), and Nagongera (rural). Annual entomological inoculation rate (aEIR) was estimated from monthly Centers for Disease Control and Prevention (CDC) light trap mosquito collections. Children aged 0.5-10 years were provided long-lasting insecticidal nets (LLINs) and followed for measures of parasite prevalence, anemia and malaria incidence. Estimates of aEIR were 2.8, 32.0, and 310 infectious bites per year, and estimates of parasite prevalence 7.4%, 9.3%, and 28.7% for Walukuba, Kihihi, and Nagongera, respectively. Over the 2-year study, malaria incidence per person-years decreased in Walukuba (0.51 versus 0.31, P = 0.001) and increased in Kihihi (0.97 versus 1.93, P < 0.001) and Nagongera (2.33 versus 3.30, P < 0.001). Of 2,582 episodes of malaria, only 8 (0.3%) met criteria for severe disease. The prevalence of anemia was low and not associated with transmission intensity. In our cohorts, where LLINs and prompt effective treatment were provided, the risk of complicated malaria and anemia was extremely low. However, malaria incidence was high and increased over time at the two rural sites, suggesting improved community-wide coverage of LLIN and additional malaria control interventions are needed in Uganda.

  6. Modeling malaria genomics reveals transmission decline and rebound in Senegal.

    PubMed

    Daniels, Rachel F; Schaffner, Stephen F; Wenger, Edward A; Proctor, Joshua L; Chang, Hsiao-Han; Wong, Wesley; Baro, Nicholas; Ndiaye, Daouda; Fall, Fatou Ba; Ndiop, Medoune; Ba, Mady; Milner, Danny A; Taylor, Terrie E; Neafsey, Daniel E; Volkman, Sarah K; Eckhoff, Philip A; Hartl, Daniel L; Wirth, Dyann F

    2015-06-02

    To study the effects of malaria-control interventions on parasite population genomics, we examined a set of 1,007 samples of the malaria parasite Plasmodium falciparum collected in Thiès, Senegal between 2006 and 2013. The parasite samples were genotyped using a molecular barcode of 24 SNPs. About 35% of the samples grouped into subsets with identical barcodes, varying in size by year and sometimes persisting across years. The barcodes also formed networks of related groups. Analysis of 164 completely sequenced parasites revealed extensive sharing of genomic regions. In at least two cases we found first-generation recombinant offspring of parents whose genomes are similar or identical to genomes also present in the sample. An epidemiological model that tracks parasite genotypes can reproduce the observed pattern of barcode subsets. Quantification of likelihoods in the model strongly suggests a reduction of transmission from 2006-2010 with a significant rebound in 2012-2013. The reduced transmission and rebound were confirmed directly by incidence data from Thiès. These findings imply that intensive intervention to control malaria results in rapid and dramatic changes in parasite population genomics. The results also suggest that genomics combined with epidemiological modeling may afford prompt, continuous, and cost-effective tracking of progress toward malaria elimination.

  7. Gut microbiota elicits a protective immune response against malaria transmission.

    PubMed

    Yilmaz, Bahtiyar; Portugal, Silvia; Tran, Tuan M; Gozzelino, Raffaella; Ramos, Susana; Gomes, Joana; Regalado, Ana; Cowan, Peter J; d'Apice, Anthony J F; Chong, Anita S; Doumbo, Ogobara K; Traore, Boubacar; Crompton, Peter D; Silveira, Henrique; Soares, Miguel P

    2014-12-04

    Glycosylation processes are under high natural selection pressure, presumably because these can modulate resistance to infection. Here, we asked whether inactivation of the UDP-galactose:β-galactoside-α1-3-galactosyltransferase (α1,3GT) gene, which ablated the expression of the Galα1-3Galβ1-4GlcNAc-R (α-gal) glycan and allowed for the production of anti-α-gal antibodies (Abs) in humans, confers protection against Plasmodium spp. infection, the causative agent of malaria and a major driving force in human evolution. We demonstrate that both Plasmodium spp. and the human gut pathobiont E. coli O86:B7 express α-gal and that anti-α-gal Abs are associated with protection against malaria transmission in humans as well as in α1,3GT-deficient mice, which produce protective anti-α-gal Abs when colonized by E. coli O86:B7. Anti-α-gal Abs target Plasmodium sporozoites for complement-mediated cytotoxicity in the skin, immediately after inoculation by Anopheles mosquitoes. Vaccination against α-gal confers sterile protection against malaria in mice, suggesting that a similar approach may reduce malaria transmission in humans.

  8. Sensitivity analysis of the age-structured malaria transmission model

    NASA Astrophysics Data System (ADS)

    Addawe, Joel M.; Lope, Jose Ernie C.

    2012-09-01

    We propose an age-structured malaria transmission model and perform sensitivity analyses to determine the relative importance of model parameters to disease transmission. We subdivide the human population into two: preschool humans (below 5 years) and the rest of the human population (above 5 years). We then consider two sets of baseline parameters, one for areas of high transmission and the other for areas of low transmission. We compute the sensitivity indices of the reproductive number and the endemic equilibrium point with respect to the two sets of baseline parameters. Our simulations reveal that in areas of either high or low transmission, the reproductive number is most sensitive to the number of bites by a female mosquito on the rest of the human population. For areas of low transmission, we find that the equilibrium proportion of infectious pre-school humans is most sensitive to the number of bites by a female mosquito. For the rest of the human population it is most sensitive to the rate of acquiring temporary immunity. In areas of high transmission, the equilibrium proportion of infectious pre-school humans and the rest of the human population are both most sensitive to the birth rate of humans. This suggests that strategies that target the mosquito biting rate on pre-school humans and those that shortens the time in acquiring immunity can be successful in preventing the spread of malaria.

  9. Highly focused anopheline breeding sites and malaria transmission in Dakar

    PubMed Central

    Machault, Vanessa; Gadiaga, Libasse; Vignolles, Cécile; Jarjaval, Fanny; Bouzid, Samia; Sokhna, Cheikh; Lacaux, Jean-Pierre; Trape, Jean-François; Rogier, Christophe; Pagès, Frédéric

    2009-01-01

    Background Urbanization has a great impact on the composition of the vector system and malaria transmission dynamics. In Dakar, some malaria cases are autochthonous but parasite rates and incidences of clinical malaria attacks have been recorded at low levels. Ecological heterogeneity of malaria transmission was investigated in Dakar, in order to characterize the Anopheles breeding sites in the city and to study the dynamics of larval density and adult aggressiveness in ten characteristically different urban areas. Methods Ten study areas were sampled in Dakar and Pikine. Mosquitoes were collected by human landing collection during four nights in each area (120 person-nights). The Plasmodium falciparum circumsporozoite (CSP) index was measured by ELISA and the entomological inoculation rates (EIR) were calculated. Open water collections in the study areas were monitored weekly for physico-chemical characterization and the presence of anopheline larvae. Adult mosquitoes and hatched larvae were identified morphologically and by molecular methods. Results In September-October 2007, 19,451 adult mosquitoes were caught among which, 1,101 were Anopheles gambiae s.l. The Human Biting Rate ranged from 0.1 bites per person per night in Yoff Village to 43.7 in Almadies. Seven out of 1,101 An. gambiae s.l. were found to be positive for P. falciparum (CSP index = 0.64%). EIR ranged from 0 infected bites per person per year in Yoff Village to 16.8 in Almadies. The An. gambiae complex population was composed of Anopheles arabiensis (94.8%) and Anopheles melas (5.2%). None of the An. melas were infected with P. falciparum. Of the 54 water collection sites monitored, 33 (61.1%) served as anopheline breeding sites on at least one observation. No An. melas was identified among the larval samples. Some physico-chemical characteristics of water bodies were associated with the presence/absence of anopheline larvae and with larval density. A very close parallel between larval and adult

  10. Optimal Control Strategy of Plasmodium vivax Malaria Transmission in Korea

    PubMed Central

    Kim, Byul Nim; Nah, Kyeongah; Chu, Chaeshin; Ryu, Sang Uk; Kang, Yong Han; Kim, Yongkuk

    2012-01-01

    Objective To investigate the optimal control strategy for Plasmodium vivax malaria transmission in Korea. Methods A Plasmodium vivax malaria transmission model with optimal control terms using a deterministic system of differential equations is presented, and analyzed mathematically and numerically. Results If the cost of reducing the reproduction rate of the mosquito population is more than that of prevention measures to minimize mosquito-human contacts, the control of mosquito-human contacts needs to be taken for a longer time, comparing the other situations. More knowledge about the actual effectiveness and costs of control intervention measures would give more realistic control strategies. Conclusion Mathematical model and numerical simulations suggest that the use of mosquito-reduction strategies is more effective than personal protection in some cases but not always. PMID:24159504

  11. Effect of rice cultivation on malaria transmission in central Kenya.

    PubMed

    Muturi, Ephantus J; Muriu, Simon; Shililu, Josephat; Mwangangi, Joseph; Jacob, Benjamin G; Mbogo, Charles; Githure, John; Novak, Robert J

    2008-02-01

    A 12-month field study was conducted between April 2004 and March 2005 to determine the association between irrigated rice cultivation and malaria transmission in Mwea, Kenya. Adult mosquitoes were collected indoors twice per month in three villages representing non-irrigated, planned, and unplanned rice agro-ecosystems and screened for blood meal sources and Plasmodium falciparum circumsporozoite proteins. Anopheles arabiensis Patton and An. funestus Giles comprised 98.0% and 1.9%, respectively, of the 39,609 female anophelines collected. Other species including An. pharoensis Theobald, An. maculipalpis Giles, An. pretoriensis Theobald, An. coustani Laveran, and An. rufipes Gough comprised the remaining 0.1%. The density of An. arabiensis was highest in the planned rice village and lowest in the non-irrigated village and that of An. funestus was significantly higher in the non-irrigated village than in irrigated ones. The human blood index (HBI) for An. arabiensis was significantly higher in the non-irrigated village compared with irrigated villages. For An. funestus, the HBI for each village differed significantly from the others, being highest in the non-irrigated village and lowest in the planned rice village. The sporozoite rate and annual entomologic inoculation rate (EIR) for An. arabiensis was 1.1% and 3.0 infective bites per person, respectively with no significant difference among villages. Sporozoite positive An. funestus were detected only in planned rice and non-irrigated villages. Overall, 3.0% of An. funestus samples tested positive for Plasmodium falciparum sporozoites. The annual EIR of 2.21 for this species in the non-irrigated village was significantly higher than 0.08 for the planned rice village. We conclude that at least in Mwea Kenya, irrigated rice cultivation may reduce the risk of malaria transmission by An. funestus but has no effect on malaria transmission by An. arabiensis. The zoophilic tendency of malaria vectors in irrigated areas

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

    PubMed Central

    Thompson, Eloise; Breil, Florence; Lorthiois, Audrey; Dupuy, Florian; Cummings, Ross; Duffier, Yoann; Corbett, Yolanda; Mercereau-Puijalon, Odile; Vernick, Kenneth; Taramelli, Donatella; Baker, David A.; Langsley, Gordon; Lavazec, Catherine

    2015-01-01

    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. PMID:25951195

  13. Rationale for short course primaquine in Africa to interrupt malaria transmission

    PubMed Central

    2012-01-01

    Following the recent successes of malaria control in sub-Saharan Africa, the gametocytocidal drug primaquine needs evaluation as a tool to further reduce the transmission of Plasmodium falciparum malaria. The drug has scarcely been used in Africa because of concerns about its safety in people with glucose-6-phosphate dehydrogenase (G6PD) deficiency. The evidence base for the use of primaquine as a transmission blocker is limited by a lack of comparable clinical and parasitological endpoints between trials. In March 2012, a group of experts met in London to discuss the existing evidence on the ability of primaquine to block malaria transmission, to define the roadblocks to the use of primaquine in Africa and to develop a roadmap to enable its rapid, safe and effective deployment. The output of this meeting is a strategic plan to optimize trial design to reach desired goals efficiently. The roadmap includes suggestions for a series of phase 1, 2, 3 and 4 studies to address specific hurdles to primaquine’s deployment. These include ex-vivo studies on efficacy, primaquine pharmacokinetics and pharmacodynamics and dose escalation studies for safety in high-risk groups. Phase 3 community trials are proposed, along with Phase 4 studies to evaluate safety, particularly in pregnancy, through pharmacovigilance in areas where primaquine is already deployed. In parallel, efforts need to be made to address issues in drug supply and regulation, to map G6PD deficiency and to support the evaluation of alternative gametocytocidal compounds. PMID:23130957

  14. Acquired transmission-blocking immunity to Plasmodium vivax in a population of southern coastal Mexico.

    PubMed

    Ramsey, J M; Salinas, E; Rodríguez, M H

    1996-05-01

    Naturally acquired transmission-blocking immunity to Plasmodium vivax was studied in three groups of patients from the southern coast of Mexico: primary cases (Group A, 61% of the study population), secondary cases with the prior infection seven or more months earlier (Group B, 23%), and secondary cases with the previous malaria experience within six months of the present study (Group C, 16%). Anopheles albimanus mosquitoes were fed with patients' infected blood cells in the presence of autologous or control serum, with or without heat-inactivation. Patients from all three groups had transmission-blocking immunity, although the quality and quantity of this blocking activity was significantly higher in the two secondary patient groups (B and C). Only primary malaria cases produced transmission-enhancing activity (23% of the cases), which was dependent on heat-labile serum components. The levels of patient group transmission-blocking immunity and mosquito infectivity were used to calculate the probabilities of a mosquito becoming infective after taking a blood meal from a P. vivax-infected patient from any one of the three groups. This probability was 0.025, with Group A patients providing the major source of these infections (92% risk from Group A and 4% risk for Groups B and C).

  15. Arbovirosis and potential transmission blocking vaccines.

    PubMed

    Londono-Renteria, Berlin; Troupin, Andrea; Colpitts, Tonya M

    2016-09-23

    Infectious diseases caused by arboviruses (viruses transmitted by arthropods) are undergoing unprecedented epidemic activity and geographic expansion. With the recent introduction of West Nile virus (1999), chikungunya virus (2013) and Zika virus (2015) to the Americas, stopping or even preventing the expansion of viruses into susceptible populations is an increasing concern. With a few exceptions, available vaccines protecting against arboviral infections are nonexistent and current disease prevention relies on vector control interventions. However, due to the emergence of and rapidly spreading insecticide resistance, different disease control methods are needed. A feasible method of reducing emerging tropical diseases is the implementation of vaccines that prevent or decrease viral infection in the vector. These vaccines are designated 'transmission blocking vaccines', or TBVs. Here, we summarize previous TBV work, discuss current research on arboviral TBVs and present several promising TBV candidates.

  16. Reduction of malaria transmission by transgenic mosquitoes expressing an antisporozoite antibody in their salivary glands.

    PubMed

    Sumitani, M; Kasashima, K; Yamamoto, D S; Yagi, K; Yuda, M; Matsuoka, H; Yoshida, S

    2013-02-01

    We have previously developed a robust salivary gland-specific expression system in transgenic Anopheles stephensi mosquitoes. To establish transgenic mosquito lines refractory to Plasmodium falciparum using this system, we generated a transgenic mosquito harbouring the gene encoding an anti-P. falciparum circumsporozoite protein (PfCSP) single-chain antibody (scFv) fused to DsRed in a secretory form (mDsRed-2A10 scFv). Fluorescence microscopy showed that the mDsRed-2A10 scFv was localized in the secretory cavities and ducts of the salivary glands in a secreted form. To evaluate P. falciparum transmission-blocking in a rodent malaria model, a transgenic Plasmodium berghei line expressing PfCSP in place of PbCSP (PfCSP/Pb) was constructed. The PfCSP/Pb parasites were able to bind to the mDsRed-2A10 scFv in the salivary glands of the transgenic mosquitoes. Importantly, the infectivity of the transgenic mosquitoes to mice was strongly impaired, indicating that the parasites had been inactivated. These results suggest that salivary gland-specific expression of antisporozoite molecules could be a promising strategy for blocking malaria transmission to humans.

  17. Cyclic GMP Balance Is Critical for Malaria Parasite Transmission from the Mosquito to the Mammalian Host

    PubMed Central

    Lakshmanan, Viswanathan; Fishbaugher, Matthew E.; Morrison, Bob; Baldwin, Michael; Macarulay, Michael; Vaughan, Ashley M.; Mikolajczak, Sebastian A.

    2015-01-01

    ABSTRACT Transmission of malaria occurs during Anopheles mosquito vector blood meals, when Plasmodium sporozoites that have invaded the mosquito salivary glands are delivered to the mammalian host. Sporozoites display a unique form of motility that is essential for their movement across cellular host barriers and invasion of hepatocytes. While the molecular machinery powering motility and invasion is increasingly well defined, the signaling events that control these essential parasite activities have not been clearly delineated. Here, we identify a phosphodiesterase (PDEγ) in Plasmodium, a regulator of signaling through cyclic nucleotide second messengers. Reverse transcriptase PCR (RT-PCR) analysis and epitope tagging of endogenous PDEγ detected its expression in blood stages and sporozoites of Plasmodium yoelii. Deletion of PDEγ (pdeγ−) rendered sporozoites nonmotile, and they failed to invade the mosquito salivary glands. Consequently, PDEγ deletion completely blocked parasite transmission by mosquito bite. Strikingly, pdeγ− sporozoites showed dramatically elevated levels of cyclic GMP (cGMP), indicating that a perturbation in cyclic nucleotide balance is involved in the observed phenotypic defects. Transcriptome sequencing (RNA-Seq) analysis of pdeγ− sporozoites revealed reduced transcript abundance of genes that encode key components of the motility and invasion apparatus. Our data reveal a crucial role for PDEγ in maintaining the cyclic nucleotide balance in the malaria parasite sporozoite stage, which in turn is essential for parasite transmission from mosquito to mammal. PMID:25784701

  18. Predicted impacts of climate change on malaria transmission in West Africa

    NASA Astrophysics Data System (ADS)

    Yamana, T. K.; Eltahir, E. A. B.

    2014-12-01

    Increases in temperature and changes in precipitation due to climate change are expected to alter the spatial distribution of malaria transmission. This is especially true in West Africa, where malaria prevalence follows the current north-south gradients in temperature and precipitation. We assess the skill of GCMs at simulating past and present climate in West Africa in order to select the most credible climate predictions for the periods 2030-2060 and 2070-2100. We then use the Hydrology, Entomology and Malaria Transmission Simulator (HYDREMATS), a mechanistic model of malaria transmission, to translate the predicted changes in climate into predicted changes availability of mosquito breeding sites, mosquito populations, and malaria prevalence. We investigate the role of acquired immunity in determining a population's response to changes in exposure to the malaria parasite.

  19. Seasonally dependent relationships between indicators of malaria transmission and disease provided by mathematical model simulations.

    PubMed

    Stuckey, Erin M; Smith, Thomas; Chitnis, Nakul

    2014-09-01

    Evaluating the effectiveness of malaria control interventions on the basis of their impact on transmission as well as impact on morbidity and mortality is becoming increasingly important as countries consider pre-elimination and elimination as well as disease control. Data on prevalence and transmission are traditionally obtained through resource-intensive epidemiological and entomological surveys that become difficult as transmission decreases. This work employs mathematical modeling to examine the relationships between malaria indicators allowing more easily measured data, such as routine health systems data on case incidence, to be translated into measures of transmission and other malaria indicators. Simulations of scenarios with different levels of malaria transmission, patterns of seasonality and access to treatment were run with an ensemble of models of malaria epidemiology and within-host dynamics, as part of the OpenMalaria modeling platform. For a given seasonality profile, regression analysis mapped simulation results of malaria indicators, such as annual average entomological inoculation rate, prevalence, incidence of uncomplicated and severe episodes, and mortality, to an expected range of values of any of the other indicators. Results were validated by comparing simulated relationships between indicators with previously published data on these same indicators as observed in malaria endemic areas. These results allow for direct comparisons of malaria transmission intensity estimates made using data collected with different methods on different indicators. They also address key concerns with traditional methods of quantifying transmission in areas of differing transmission intensity and sparse data. Although seasonality of transmission is often ignored in data compilations, the models suggest it can be critically important in determining the relationship between transmission and disease. Application of these models could help public health officials

  20. The Influence of Dams on Malaria Transmission in Sub-Saharan Africa.

    PubMed

    Kibret, Solomon; Wilson, G Glenn; Ryder, Darren; Tekie, Habte; Petros, Beyene

    2015-04-18

    The construction of dams in sub-Saharan Africa is pivotal for food security and alleviating poverty in the region. However, the unintended adverse public health implications of extending the spatial distribution of water infrastructure are poorly documented and may minimize the intended benefits of securing water supplies. This paper reviews existing studies on the influence of dams on the spatial distribution of malaria parasites and vectors in sub-Saharan Africa. Common themes emerging from the literature were that dams intensified malaria transmission in semi-arid and highland areas with unstable malaria transmission but had little or no impact in areas with perennial transmission. Differences in the impacts of dams resulted from the types and characteristics of malaria vectors and their breeding habitats in different settings of sub-Saharan Africa. A higher abundance of a less anthropophilic Anopheles arabiensis than a highly efficient vector A. gambiae explains why dams did not increase malaria in stable areas. In unstable areas where transmission is limited by availability of water bodies for vector breeding, dams generally increase malaria by providing breeding habitats for prominent malaria vector species. Integrated vector control measures that include reservoir management, coupled with conventional malaria control strategies, could optimize a reduction of the risk of malaria transmission around dams in the region.

  1. The Role of Rainfall Patterns in Seasonal Malaria Transmission

    NASA Astrophysics Data System (ADS)

    Bomblies, A.

    2010-12-01

    Seasonal total precipitation is well known to affect malaria transmission because Anopheles mosquitoes depend on standing water for breeding habitat. However, the within-season temporal pattern of the rainfall influences persistence of standing water and thus rainfall patterns also affect mosquito population dynamics. In this talk, I show that intraseasonal rainfall pattern describes 40% of the variance in simulated mosquito abundance in a Niger Sahel village where malaria is endemic but highly seasonal, demonstrating the necessity for detailed distributed hydrology modeling to explain the variance from this important effect. I apply a field validated, high spatial- and temporal-resolution hydrology model coupled with an entomology model. Using synthetic rainfall time series generated using a stationary first-order Markov Chain model, I hold all variables except hourly rainfall constant, thus isolating the contribution of rainfall pattern to variance in mosquito abundance. I further show the utility of hydrology modeling to assess precipitation effects by analyzing collected water. Time-integrated surface area of pools explains 70% of the variance in mosquito abundance, and time-integrated surface area of pools persisting longer than seven days explains 82% of the variance, showing an improved predictive ability when pool persistence is explicitly modeled at high spatio-temporal resolution. I extend this analysis to investigate the impacts of this effect on malaria vector mosquito populations under climate shift scenarios, holding all climate variables except precipitation constant. In these scenarios, rainfall mean and variance change with climatic change, and the modeling approach evaluates the impact of non-stationarity in rainfall and the associated rainfall patterns on expected mosquito activity.

  2. Conditions of malaria transmission in Dakar from 2007 to 2010

    PubMed Central

    2011-01-01

    Background Previous studies in Dakar have highlighted the spatial and temporal heterogeneity of Anopheles gambiae s.l. biting rates. In order to improve the knowledge of the determinants of malaria transmission in this city, the present study reports the results of an extensive entomological survey that was conducted in 45 areas in Dakar from 2007 to 2010. Methods Water collections were monitored for the presence of anopheline larvae. Adult mosquitoes were sampled by human landing collection. Plasmodium falciparum circumsporozoïte (CSP) protein indexes were measured by ELISA (enzyme-linked immunosorbent assay), and the entomological inoculation rates were calculated. Results The presence of anopheline larvae were recorded in 1,015 out of 2,683 observations made from 325 water collections. A water pH of equal to or above 8.0, a water temperature that was equal to or above 30°C, the absence of larvivorous fishes, the wet season, the presence of surface vegetation, the persistence of water and location in a slightly urbanised area were significantly associated with the presence of anopheline larvae and/or with a higher density of anopheline larvae. Most of the larval habitats were observed in public areas, i.e., freely accessible. A total of 496,310 adult mosquitoes were caught during 3096 person-nights, and 44967 of these specimens were identified as An.gambiae s.l. The mean An. gambiae s.l. human-biting rate ranged from 0.1 to 248.9 bites per person per night during the rainy season. Anopheles arabiensis (93.14%), Anopheles melas (6.83%) and An. gambiae s.s. M form (0.03%) were the three members of the An. gambiae complex. Fifty-two An. arabiensis and two An. melas specimens were CSP-positive, and the annual CSP index was 0.64% in 2007, 0.09% in 2008-2009 and 0.12% in 2009-2010. In the studied areas, the average EIR ranged from 0 to 17.6 infected bites per person during the entire transmission season. Conclusion The spatial and temporal heterogeneity of An

  3. Vaccines against malaria.

    PubMed

    Ouattara, Amed; Laurens, Matthew B

    2015-03-15

    Despite global efforts to control malaria, the illness remains a significant public health threat. Currently, there is no licensed vaccine against malaria, but an efficacious vaccine would represent an important public health tool for successful malaria elimination. Malaria vaccine development continues to be hindered by a poor understanding of antimalarial immunity, a lack of an immune correlate of protection, and the genetic diversity of malaria parasites. Current vaccine development efforts largely target Plasmodium falciparum parasites in the pre-erythrocytic and erythrocytic stages, with some research on transmission-blocking vaccines against asexual stages and vaccines against pregnancy-associated malaria. The leading pre-erythrocytic vaccine candidate is RTS,S, and early results of ongoing Phase 3 testing show overall efficacy of 46% against clinical malaria. The next steps for malaria vaccine development will focus on the design of a product that is efficacious against the highly diverse strains of malaria and the identification of a correlate of protection against disease.

  4. Artesunate-tafenoquine combination therapy promotes clearance and abrogates transmission of the avian malaria parasite Plasmodium gallinaceum.

    PubMed

    Tasai, Suchada; Saiwichai, Tawee; Kaewthamasorn, Morakot; Tiawsirisup, Sonthaya; Buddhirakkul, Prayute; Chaichalotornkul, Sirintip; Pattaradilokrat, Sittiporn

    2017-01-15

    Clinical manifestations of malaria infection in vertebrate hosts arise from the multiplication of the asexual stage parasites in the blood, while the gametocytes are responsible for the transmission of the disease. Antimalarial drugs that target the blood stage parasites and transmissible gametocytes are rare, but are essentially needed for the effective control of malaria and for limiting the spread of resistance. Artemisinin and its derivatives are the current first-line antimalarials that are effective against the blood stage parasites and gametocytes, but resistance to artemisinin has now emerged and spread in various malaria endemic areas. Therefore, a novel antimalarial drug, or a new drug combination, is critically needed to overcome this problem. The objectives of this study were to evaluate the efficacy of a relatively new antimalarial compound, tafenoquine (TQ), and a combination of TQ and a low dose of artesunate (ATN) on the in vivo blood stage multiplication, gametocyte development and transmission of the avian malaria parasite Plasmodium gallinaceum to the vector Aedes aegypti. The results showed that a 5-d treatment with TQ alone was unable to clear the blood stage parasites, but was capable of reducing the mortality rate, while TQ monotherapy at a high dose of 30mg/kg was highly effective against the gametocytes and completely blocked the transmission of P. gallinaceum. In addition, the combination therapy of TQ+ATN completely cleared P. gallinaceum blood stages and sped up the gametocyte clearance from chickens, suggesting the synergistic effect of the two drugs. In conclusion, TQ is demonstrated to be effective for limiting avian malaria transmission and may be used in combination with a low dose of ATN for safe and effective treatment.

  5. Threshold dynamics of a malaria transmission model in periodic environment

    NASA Astrophysics Data System (ADS)

    Wang, Lei; Teng, Zhidong; Zhang, Tailei

    2013-05-01

    In this paper, we propose a malaria transmission model with periodic environment. The basic reproduction number R0 is computed for the model and it is shown that the disease-free periodic solution of the model is globally asymptotically stable when R0<1, that is, the disease goes extinct when R0<1, while the disease is uniformly persistent and there is at least one positive periodic solution when R0>1. It indicates that R0 is the threshold value determining the extinction and the uniform persistence of the disease. Finally, some examples are given to illustrate the main theoretical results. The numerical simulations show that, when the disease is uniformly persistent, different dynamic behaviors may be found in this model, such as the global attractivity and the chaotic attractor.

  6. The incidence of malaria in travellers to South-East Asia: is local malaria transmission a useful risk indicator?

    PubMed Central

    2010-01-01

    Background The presence of ongoing local malaria transmission, identified though local surveillance and reported to regional WHO offices, by S-E Asian countries, forms the basis of national and international chemoprophylaxis recommendations in western countries. The study was designed to examine whether the strategy of using malaria transmission in a local population was an accurate estimate of the malaria threat faced by travellers and a correlate of malaria in returning travellers. Methods Malaria endemicity was described from distribution and intensity in the local populations of ten S-E Asian destination countries over the period 2003-2008 from regionally reported cases to WHO offices. Travel acquired malaria was collated from malaria surveillance reports from the USA and 12 European countries over the same period. The numbers of travellers visiting the destination countries was based on immigration and tourism statistics collected on entry of tourists to the destination countries. Results In the destination countries, mean malaria rates in endemic countries ranged between 0.01 in Korea to 4:1000 population per year in Lao PDR, with higher regional rates in a number of countries. Malaria cases imported into the 13 countries declined by 47% from 140 cases in 2003 to 66 in 2008. A total of 608 cases (27.3% Plasmodium falciparum (Pf)) were reported over the six years, the largest number acquired in Indonesia, Thailand and Korea. Four countries had an incidence > 1 case per 100,000 traveller visits; Burma (Myanmar), Indonesia, Cambodia and Laos (range 1 to 11.8-case per 100,000 visits). The remaining six countries rates were < 1 case per 100,000 visits. The number of visitors arriving from source countries increased by 60% from 8.5 Million to 13.6 million over the 6 years. Conclusion The intensity of malaria transmission particularly sub-national activity did not correlate with the risk of travellers acquiring malaria in the large numbers of arriving visitors. It

  7. Insecticide-Treated Net Campaign and Malaria Transmission in Western Kenya: 2003–2015

    PubMed Central

    Zhou, Guofa; Lee, Ming-Chieh; Githeko, Andrew K.; Atieli, Harrysone E.; Yan, Guiyun

    2016-01-01

    Insecticide-treated nets (ITNs) are among the three major intervention measures that have reduced malaria transmission in the past decade. However, increased insecticide resistance in vectors, together with outdoor transmission, has limited the efficacy of the ITN scaling-up efforts. Observations on longitudinal changes in ITN coverage and its impact on malaria transmission allow policy makers to make informed adjustments to control strategies. We analyzed field surveys on ITN ownership, malaria parasite prevalence, and malaria vector population dynamics in seven sentinel sites in western Kenya from 2003 to 2015. We found that ITN ownership has increased from an average of 18% in 2003 to 85% in 2015. Malaria parasite prevalence in school children decreased by about 70% from 2003 to 2008 (the first mass distribution of free ITNs was in 2006) but has resurged by >50% since then. At the community level, use of ITNs reduced infections by 23% in 2008 and 43% in 2010, although the reduction was down to 25% in 2011. The indoor-resting density of the predominant vector, Anopheles gambiae, has been suppressed since 2007; however, Anopheles funestus populations have resurged and have increased 20-fold in some places since 2007. In conclusion, there is limited room for further increase in ITN coverage in western Kenya. The rebounding in malaria transmission highlights the urgent need of new or improved malaria control interventions so as to further reduce malaria transmission. PMID:27574601

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

    PubMed Central

    2012-01-01

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

  9. Epidemic and Endemic Malaria Transmission Related to Fish Farming Ponds in the Amazon Frontier

    PubMed Central

    Barcellos, Christovam; Kitron, Uriel; Camara, Daniel Cardoso Portela; Pereira, Glaucio Rocha; Keppeler, Erlei Cassiano; da Silva-Nunes, Mônica

    2015-01-01

    Fish farming in the Amazon has been stimulated as a solution to increase economic development. However, poorly managed fish ponds have been sometimes associated with the presence of Anopheles spp. and consequently, with malaria transmission. In this study, we analyzed the spatial and temporal dynamics of malaria in the state of Acre (and more closely within a single county) to investigate the potential links between aquaculture and malaria transmission in this region. At the state level, we classified the 22 counties into three malaria endemicity patterns, based on the correlation between notification time series. Furthermore, the study period (2003–2013) was divided into two phases (epidemic and post-epidemic). Higher fish pond construction coincided both spatially and temporally with increased rate of malaria notification. Within one malaria endemic county, we investigated the relationship between the geolocation of malaria cases (2011–2012) and their distance to fish ponds. Entomological surveys carried out in these ponds provided measurements of anopheline abundance that were significantly associated with the abundance of malaria cases within 100 m of the ponds (P < 0.005; r = 0.39). These results taken together suggest that fish farming contributes to the maintenance of high transmission levels of malaria in this region. PMID:26361330

  10. Transmission Risk from Imported Plasmodium vivax Malaria in the China-Myanmar Border Region.

    PubMed

    Wang, Duoquan; Li, Shengguo; Cheng, Zhibin; Xiao, Ning; Cotter, Chris; Hwang, Jimee; Li, Xishang; Yin, Shouqin; Wang, Jiazhi; Bai, Liang; Zheng, Zhi; Wang, Sibao

    2015-10-01

    Malaria importation and local vector susceptibility to imported Plasmodium vivax infection are a continuing risk along the China-Myanmar border. Malaria transmission has been prevented in 3 border villages in Tengchong County, Yunnan Province, China, by use of active fever surveillance, integrated vector control measures, and intensified surveillance and response.

  11. Comparison of Intranasal Outer Membrane Vesicles with Cholera Toxin and Injected MF59C.1 as Adjuvants for Malaria Transmission Blocking Antigens AnAPN1 and Pfs48/45

    PubMed Central

    Pritsch, Michael; Ben-Khaled, Najib; Chaloupka, Michael; Kobold, Sebastian; Berens-Riha, Nicole; Peter, Annabell; Liegl, Gabriele; Schubert, Sören; Hoelscher, Michael; Löscher, Thomas; Wieser, Andreas

    2016-01-01

    Purified protein vaccines often require adjuvants for efficient stimulation of immune responses. There is no licensed mucosal adjuvant on the market to adequately boost the immune response to purified antigens for intranasal applications in humans. Bacterial outer membrane vesicles (OMV) are attractive candidates potentially combining antigenic and adjuvant properties in one substance. To more precisely characterize the potential of Escherichia coli OMV for intranasal vaccination with heterologous antigens, immune responses for AnAPN1 and Pfs48/45 as well as ovalbumin as a reference antigen were assessed in mice. The intranasal adjuvant cholera toxin (CT) and parenteral adjuvant MF59C.1 were used in comparison. Vaccinations were administered intranasally or subcutaneously. Antibodies (total IgG and IgM as well as subclasses IgG1, IgG2a, IgG2b, and IgG3) were measured by ELISA. T cell responses (cytotoxic T cells, Th1, Th17, and regulatory T cells) were determined by flow cytometry. When OMV were used as adjuvant for intranasal immunization, antibody and cellular responses against all three antigens could be induced, comparable to cholera toxin and MF59C.1. Antigen-specific IgG titres above 1 : 105 could be detected in all groups. This study provides the rationale for further development of OMV as a vaccination strategy in malaria and other diseases. PMID:27239480

  12. Forest malaria in Bangladesh. II. Transmission by Anopheles dirus.

    PubMed

    Rosenberg, R; Maheswary, N P

    1982-03-01

    Seasonal, holoendemic malaria transmission in a small, isolated forest community was studied by doing outdoor and indoor all-night man-biting catches over 21 consecutive months. More than 3.8% of Anopheles dirus (=An. balabacensis s.l.), the most frequently caught anopheline, were infective. One An. annularis was also infective. Transmission occurred only during the 7-month monsoon. In the absence of DDT, An. dirus bit with equal frequency indoors and outdoors. When DDT was present in dwellings, fewer females fed indoors and they fed earlier. Feeding pattern was influenced by the phase of the moon: peak outdoors feeding was sharpest and earliest at first quarter and came later as the moon rose later. An average 31% of biting An. dirus lived long enough to reach infectivity of P. falciparum. Although fewer than 10 females fed per man per night, a resident could have received more than 100 infective bites in 2 years. Correlation between actual and calculated rates of gametocytemia were poorest in months when calculated survival rates of mosquitoes were most suspect.

  13. Optimal temperature for malaria transmission is dramatically lower than previously predicted

    USGS Publications Warehouse

    Mordecai, Erin A.; Paaijmans, Krijn P.; Johnson, Leah R.; Balzer, Christian; Ben-Horin, Tal; de Moor, Emily; McNally, Amy; Pawar, Samraat; Ryan, Sadie J.; Smith, Thomas C.; Lafferty, Kevin D.

    2013-01-01

    The ecology of mosquito vectors and malaria parasites affect the incidence, seasonal transmission and geographical range of malaria. Most malaria models to date assume constant or linear responses of mosquito and parasite life-history traits to temperature, predicting optimal transmission at 31 °C. These models are at odds with field observations of transmission dating back nearly a century. We build a model with more realistic ecological assumptions about the thermal physiology of insects. Our model, which includes empirically derived nonlinear thermal responses, predicts optimal malaria transmission at 25 °C (6 °C lower than previous models). Moreover, the model predicts that transmission decreases dramatically at temperatures > 28 °C, altering predictions about how climate change will affect malaria. A large data set on malaria transmission risk in Africa validates both the 25 °C optimum and the decline above 28 °C. Using these more accurate nonlinear thermal-response models will aid in understanding the effects of current and future temperature regimes on disease transmission.

  14. Ethics, economics, and the use of primaquine to reduce falciparum malaria transmission in asymptomatic populations.

    PubMed

    Lubell, Yoel; White, Lisa; Varadan, Sheila; Drake, Tom; Yeung, Shunmay; Cheah, Phaik Yeong; Maude, Richard J; Dondorp, Arjen; Day, Nicholas P J; White, Nicholas J; Parker, Michael

    2014-08-01

    Yoel Lubell and colleagues consider ethical and economic perspectives on mass drug administration of primaquine to limit transmission of P. falciparum malaria. Please see later in the article for the Editors' Summary.

  15. Urban Malaria: Understanding its Epidemiology, Ecology, and Transmission across Seven Diverse ICEMR Network Sites

    PubMed Central

    Wilson, Mark L.; Krogstad, Donald J.; Arinaitwe, Emmanuel; Arevalo-Herrera, Myriam; Chery, Laura; Ferreira, Marcelo U.; Ndiaye, Daouda; Mathanga, Don P.; Eapen, Alex

    2015-01-01

    A major public health question is whether urbanization will transform malaria from a rural to an urban disease. However, differences about definitions of urban settings, urban malaria, and whether malaria control should differ between rural and urban areas complicate both the analysis of available data and the development of intervention strategies. This report examines the approach of the International Centers of Excellence for Malaria Research (ICEMR) to urban malaria in Brazil, Colombia, India (Chennai and Goa), Malawi, Senegal, and Uganda. Its major theme is the need to determine whether cases diagnosed in urban areas were imported from surrounding rural areas or resulted from transmission within the urban area. If infections are being acquired within urban areas, malaria control measures must be targeted within those urban areas to be effective. Conversely, if malaria cases are being imported from rural areas, control measures must be directed at vectors, breeding sites, and infected humans in those rural areas. Similar interventions must be directed differently if infections were acquired within urban areas. The hypothesis underlying the ICEMR approach to urban malaria is that optimal control of urban malaria depends on accurate epidemiologic and entomologic information about transmission. PMID:26259941

  16. Urban Malaria: Understanding its Epidemiology, Ecology, and Transmission Across Seven Diverse ICEMR Network Sites.

    PubMed

    Wilson, Mark L; Krogstad, Donald J; Arinaitwe, Emmanuel; Arevalo-Herrera, Myriam; Chery, Laura; Ferreira, Marcelo U; Ndiaye, Daouda; Mathanga, Don P; Eapen, Alex

    2015-09-01

    A major public health question is whether urbanization will transform malaria from a rural to an urban disease. However, differences about definitions of urban settings, urban malaria, and whether malaria control should differ between rural and urban areas complicate both the analysis of available data and the development of intervention strategies. This report examines the approach of the International Centers of Excellence for Malaria Research (ICEMR) to urban malaria in Brazil, Colombia, India (Chennai and Goa), Malawi, Senegal, and Uganda. Its major theme is the need to determine whether cases diagnosed in urban areas were imported from surrounding rural areas or resulted from transmission within the urban area. If infections are being acquired within urban areas, malaria control measures must be targeted within those urban areas to be effective. Conversely, if malaria cases are being imported from rural areas, control measures must be directed at vectors, breeding sites, and infected humans in those rural areas. Similar interventions must be directed differently if infections were acquired within urban areas. The hypothesis underlying the ICEMR approach to urban malaria is that optimal control of urban malaria depends on accurate epidemiologic and entomologic information about transmission.

  17. International Funding for Malaria Control in Relation to Populations at Risk of Stable Plasmodium falciparum Transmission

    PubMed Central

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

    2008-01-01

    Background The international financing of malaria control has increased significantly in the last ten years in parallel with calls to halve the malaria burden by the year 2015. The allocation of funds to countries should reflect the size of the populations at risk of infection, disease, and death. To examine this relationship, we compare an audit of international commitments with an objective assessment of national need: the population at risk of stable Plasmodium falciparum malaria transmission in 2007. Methods and Findings The national distributions of populations at risk of stable P. falciparum transmission were projected to the year 2007 for each of 87 P. falciparum–endemic countries. Systematic online- and literature-based searches were conducted to audit the international funding commitments made for malaria control by major donors between 2002 and 2007. These figures were used to generate annual malaria funding allocation (in US dollars) per capita population at risk of stable P. falciparum in 2007. Almost US$1 billion are distributed each year to the 1.4 billion people exposed to stable P. falciparum malaria risk. This is less than US$1 per person at risk per year. Forty percent of this total comes from the Global Fund to Fight AIDS, Tuberculosis and Malaria. Substantial regional and national variations in disbursements exist. While the distribution of funds is found to be broadly appropriate, specific high population density countries receive disproportionately less support to scale up malaria control. Additionally, an inadequacy of current financial commitments by the international community was found: under-funding could be from 50% to 450%, depending on which global assessment of the cost required to scale up malaria control is adopted. Conclusions Without further increases in funding and appropriate targeting of global malaria control investment it is unlikely that international goals to halve disease burdens by 2015 will be achieved. Moreover, the

  18. Effect of Transmission Setting and Mixed Species Infections on Clinical Measures of Malaria in Malawi

    PubMed Central

    Bruce, Marian C.; Macheso, Allan; Kelly-Hope, Louise A.; Nkhoma, Standwell; McConnachie, Alex; Molyneux, Malcolm E.

    2008-01-01

    Background In malaria endemic regions people are commonly infected with multiple species of malaria parasites but the clinical impact of these Plasmodium co-infections is unclear. Differences in transmission seasonality and transmission intensity between endemic regions have been suggested as important factors in determining the effect of multiple species co-infections. Principal Findings In order to investigate the impact of multiple-species infections on clinical measures of malaria we carried out a cross-sectional community survey in Malawi, in 2002. We collected clinical and parasitological data from 2918 participants aged >6 months, and applied a questionnaire to measure malaria morbidity. We examined the effect of transmission seasonality and intensity on fever, history of fever, haemoglobin concentration ([Hb]) and parasite density, by comparing three regions: perennial transmission (PT), high intensity seasonal transmission (HIST) and low intensity seasonal transmission (LIST). These regions were defined using multi-level modelling of PCR prevalence data and spatial and geo-climatic measures. The three Plasmodium species (P. falciparum, P. malariae and P. ovale) were randomly distributed amongst all children but not adults in the LIST and PT regions. Mean parasite density in children was lower in the HIST compared with the other two regions. Mixed species infections had lower mean parasite density compared with single species infections in the PT region. Fever rates were similar between transmission regions and were unaffected by mixed species infections. A history of fever was associated with single species infections but only in the HIST region. Reduced mean [Hb] and increased anaemia was associated with perennial transmission compared to seasonal transmission. Children with mixed species infections had higher [Hb] in the HIST region. Conclusions Our study suggests that the interaction of Plasmodium co-infecting species can have protective effects against

  19. The Limits and Intensity of Plasmodium falciparum Transmission: Implications for Malaria Control and Elimination Worldwide

    PubMed Central

    Guerra, Carlos A; Gikandi, Priscilla W; Tatem, Andrew J; Noor, Abdisalan M; Smith, Dave L; Hay, Simon I; Snow, Robert W

    2008-01-01

    Background The efficient allocation of financial resources for malaria control using appropriate combinations of interventions requires accurate information on the geographic distribution of malaria risk. An evidence-based description of the global range of Plasmodium falciparum malaria and its endemicity has not been assembled in almost 40 y. This paper aims to define the global geographic distribution of P. falciparum malaria in 2007 and to provide a preliminary description of its transmission intensity within this range. Methods and Findings The global spatial distribution of P. falciparum malaria was generated using nationally reported case-incidence data, medical intelligence, and biological rules of transmission exclusion, using temperature and aridity limits informed by the bionomics of dominant Anopheles vector species. A total of 4,278 spatially unique cross-sectional survey estimates of P. falciparum parasite rates were assembled. Extractions from a population surface showed that 2.37 billion people lived in areas at any risk of P. falciparum transmission in 2007. Globally, almost 1 billion people lived under unstable, or extremely low, malaria risk. Almost all P. falciparum parasite rates above 50% were reported in Africa in a latitude band consistent with the distribution of Anopheles gambiae s.s. Conditions of low parasite prevalence were also common in Africa, however. Outside of Africa, P. falciparum malaria prevalence is largely hypoendemic (less than 10%), with the median below 5% in the areas surveyed. Conclusions This new map is a plausible representation of the current extent of P. falciparum risk and the most contemporary summary of the population at risk of P. falciparum malaria within these limits. For 1 billion people at risk of unstable malaria transmission, elimination is epidemiologically feasible, and large areas of Africa are more amenable to control than appreciated previously. The release of this information in the public domain will

  20. Ikonos-derived malaria transmission risk in northwestern Thailand.

    PubMed

    Sithiprasasna, Ratana; Ugsang, Donald M; Honda, Kiyoshi; Jones, James W; Singhasivanon, Pratap

    2005-01-01

    We mapped overall malaria cases and located each field observed major malaria vector breeding habitat using Global Positioning System (GPS) instruments from September 2000 to October 2003 around the three malaria-endemic villages of Ban Khun Huay, Ban Pa Dae, and Ban Tham Seau, Mae Sod district, Tak Province, Thailand. The land-use/land-cover classifications of the three villages and surrounding areas were performed on IKONOS satellite images acquired on 12 November 2001 with a spatial resolution of 1 x 1 m. Stream network was delineated and displayed. Proximity analysis was performed on the locations of the houses with and without malaria cases within a 1.5 km buffer from An. minimus immature mosquito breeding habitats, mainly stream margins. The 1.5 km used in our proximity analysis was arbitrarily estimated based on the An. minimus flight range. A statistical t-test at 5% significance level was performed to evaluate whether houses with malaria cases have higher proximities to streams than houses without malaria cases. The result shows no significant difference between proximity to streams between houses with malaria cases and houses without malaria cases. We suspect that the actual flight range of An. minimus may be greater than 1.5 km. The An. minimus larval habitat deserves more detailed investigation. Further studies on human behavior contrary to that required for adequate malaria control among these three villages are also recommended.

  1. Activity of Herbal Medicines on Plasmodium falciparum Gametocytes: Implications for Malaria Transmission in Ghana

    PubMed Central

    Amoah, Linda Eva; Kakaney, Courage; Kwansa-Bentum, Bethel; Kusi, Kwadwo Asamoah

    2015-01-01

    Background Malaria still remains a major health issue in Ghana despite the introduction of Artemisinin-based combination therapy (ACT) coupled with other preventative measures such as the use of insecticide treated nets (ITNs). The global quest for eradication of malaria has heightened the interest of identifying drugs that target the sexual stage of the parasite, referred to as transmission-blocking drugs. This study aimed at assessing the efficacy and gametocydal effects of some commonly used herbal malaria products in Ghana. Methodology/Principal Findings After identifying herbal anti-malarial products frequently purchased on the Ghanaian market, ten of them were selected and lyophilized. In vitro drug sensitivity testing of different concentrations of the herbal products was carried out on asexual and in vitro generated gametocytes of the 3D7 strain of Plasmodium falciparum. The efficacies of the products were assessed by microscopy. Cultures containing low dose of RT also produced the least number of late stage gametocytes. Two of the herbal products CM and RT inhibited the growth of late stage gametocytes by > 80% at 100 μg/ml whilst KG was the most inhibitory to early stage gametocytes at that same concentration. However at 1 μg/ml, only YF significantly inhibited the survival of late stage gametocytes although at that same concentration YF barely inhibited the survival of early stage gametocytes. Conclusions/Significance Herbal product RT (Aloe schweinfurthii, Khaya senegalensis, Piliostigma thonningii and Cassia siamea) demonstrated properties of a highly efficacious gametocydal product. Low dose of herbal product RT exhibited the highest gametocydal activity and at 100 μg/ml, RT exhibited >80% inhibition of late stage gametocytes. However inhibition of asexual stage parasite by RT was not optimal. Improving the asexual inhibition of RT could convert RT into an ideal antimalarial herbal product. We also found that generally C. sanguinolenta containing

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

    PubMed

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

    2015-02-01

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

  3. Purification Methodology for Viable and Infective Plasmodium vivax Gametocytes That Is Compatible with Transmission-Blocking Assays

    PubMed Central

    Vera, Omaira; Brelas de Brito, Paula; Albrecht, Letusa; Martins-Campos, Keillen Monick; Pimenta, Paulo F. P.; Monteiro, Wuelton M.; Lacerda, Marcus V. G.

    2015-01-01

    Significant progress toward the control of malaria has been achieved, especially regarding Plasmodium falciparum infections. However, the unique biology of Plasmodium vivax hampers current control strategies. The early appearance of P. vivax gametocytes in the peripheral blood and the impossibility of culturing this parasite are major drawbacks. Using blood samples from 40 P. vivax-infected patients, we describe here a methodology to purify viable gametocytes and further infect anophelines. This method opens new avenues to validate transmission-blocking strategies. PMID:26239989

  4. Antibody acquisition models: A new tool for serological surveillance of malaria transmission intensity

    PubMed Central

    Yman, Victor; White, Michael T.; Rono, Josea; Arcà, Bruno; Osier, Faith H.; Troye-Blomberg, Marita; Boström, Stéphanie; Ronca, Raffaele; Rooth, Ingegerd; Färnert, Anna

    2016-01-01

    Serology has become an increasingly important tool for the surveillance of a wide range of infectious diseases. It has been particularly useful to monitor malaria transmission in elimination settings where existing metrics such as parasite prevalence and incidence of clinical cases are less sensitive. Seroconversion rates, based on antibody prevalence to Plasmodium falciparum asexual blood-stage antigens, provide estimates of transmission intensity that correlate with entomological inoculation rates but lack precision in settings where seroprevalence is still high. Here we present a new and widely applicable method, based on cross-sectional data on individual antibody levels. We evaluate its use as a sero-surveillance tool in a Tanzanian setting with declining malaria prevalence. We find that the newly developed mathematical models produce more precise estimates of transmission patterns, are robust in high transmission settings and when sample sizes are small, and provide a powerful tool for serological evaluation of malaria transmission intensity. PMID:26846726

  5. A semi-automated luminescence based standard membrane feeding assay identifies novel small molecules that inhibit transmission of malaria parasites by mosquitoes.

    PubMed

    Vos, Martijn W; Stone, Will J R; Koolen, Karin M; van Gemert, Geert-Jan; van Schaijk, Ben; Leroy, Didier; Sauerwein, Robert W; Bousema, Teun; Dechering, Koen J

    2015-12-21

    Current first-line treatments for uncomplicated falciparum malaria rapidly clear the asexual stages of the parasite, but do not fully prevent parasite transmission by mosquitoes. The standard membrane feeding assay (SMFA) is the biological gold standard assessment of transmission reducing activity (TRA), but its throughput is limited by the need to determine mosquito infection status by dissection and microscopy. Here we present a novel dissection-free luminescence based SMFA format using a transgenic Plasmodium falciparum reporter parasite without resistance to known antimalarials and therefore unrestricted in its utility in compound screening. Analyses of sixty-five compounds from the Medicines for Malaria Venture validation and malaria boxes identified 37 compounds with high levels of TRA (>80%); different assay modes allowed discrimination between gametocytocidal and downstream modes of action. Comparison of SMFA data to published assay formats for predicting parasite infectivity indicated that individual in vitro screens show substantial numbers of false negatives. These results highlight the importance of the SMFA in the screening pipeline for transmission reducing compounds and present a rapid and objective method. In addition we present sixteen diverse chemical scaffolds from the malaria box that may serve as a starting point for further discovery and development of malaria transmission blocking drugs.

  6. A semi-automated luminescence based standard membrane feeding assay identifies novel small molecules that inhibit transmission of malaria parasites by mosquitoes

    PubMed Central

    Vos, Martijn W.; Stone, Will J. R.; Koolen, Karin M.; van Gemert, Geert-Jan; van Schaijk, Ben; Leroy, Didier; Sauerwein, Robert W.; Bousema, Teun; Dechering, Koen J.

    2015-01-01

    Current first-line treatments for uncomplicated falciparum malaria rapidly clear the asexual stages of the parasite, but do not fully prevent parasite transmission by mosquitoes. The standard membrane feeding assay (SMFA) is the biological gold standard assessment of transmission reducing activity (TRA), but its throughput is limited by the need to determine mosquito infection status by dissection and microscopy. Here we present a novel dissection-free luminescence based SMFA format using a transgenic Plasmodium falciparum reporter parasite without resistance to known antimalarials and therefore unrestricted in its utility in compound screening. Analyses of sixty-five compounds from the Medicines for Malaria Venture validation and malaria boxes identified 37 compounds with high levels of TRA (>80%); different assay modes allowed discrimination between gametocytocidal and downstream modes of action. Comparison of SMFA data to published assay formats for predicting parasite infectivity indicated that individual in vitro screens show substantial numbers of false negatives. These results highlight the importance of the SMFA in the screening pipeline for transmission reducing compounds and present a rapid and objective method. In addition we present sixteen diverse chemical scaffolds from the malaria box that may serve as a starting point for further discovery and development of malaria transmission blocking drugs. PMID:26687564

  7. A climate-based distribution model of malaria transmission in sub-Saharan Africa.

    PubMed

    Craig, M H; Snow, R W; le Sueur, D

    1999-03-01

    Malaria remains the single largest threat to child survival in sub-Saharan Africa and warrants long-term investment for control. Previous malaria distribution maps have been vague and arbitrary. Marlies Craig, Bob Snow and David le Sueur here describe a simple numerical approach to defining distribution of malaria transmission, based upon biological constraints of climate on parasite and vector development. The model compared well with contemporary field data and historical 'expert opinion' maps, excepting small-scale ecological anomalies. The model provides a numerical basis for further refinement and prediction of the impact of climate change on transmission. Together with population, morbidity and mortality data, the model provides a fundamental tool for strategic control of malaria.

  8. Application of satellite estimates of rainfall distribution to simulate the potential for malaria transmission in Africa

    NASA Astrophysics Data System (ADS)

    Yamana, T. K.; Eltahir, E. A.

    2009-12-01

    The Hydrology, Entomology and Malaria Transmission Simulator (HYDREMATS) is a mechanistic model developed to assess malaria risk in areas where the disease is water-limited. This model relies on precipitation inputs as its primary forcing. Until now, applications of the model have used ground-based precipitation observations. However, rain gauge networks in the areas most affected by malaria are often sparse. The increasing availability of satellite based rainfall estimates could greatly extend the range of the model. The minimum temporal resolution of precipitation data needed was determined to be one hour. The CPC Morphing technique (CMORPH ) distributed by NOAA fits this criteria, as it provides 30-minute estimates at 8km resolution. CMORPH data were compared to ground observations in four West African villages, and calibrated to reduce overestimation and false alarm biases. The calibrated CMORPH data were used to force HYDREMATS, resulting in outputs for mosquito populations, vectorial capacity and malaria transmission.

  9. Salinomycin and Other Ionophores as a New Class of Antimalarial Drugs with Transmission-Blocking Activity

    PubMed Central

    D'Alessandro, Sarah; Corbett, Yolanda; Ilboudo, Denise P.; Misiano, Paola; Dahiya, Nisha; Abay, Solomon M.; Habluetzel, Annette; Grande, Romualdo; Gismondo, Maria R.; Dechering, Koen J.; Koolen, Karin M. J.; Sauerwein, Robert W.; Taramelli, Donatella; Parapini, Silvia

    2015-01-01

    The drug target profile proposed by the Medicines for Malaria Venture for a malaria elimination/eradication policy focuses on molecules active on both asexual and sexual stages of Plasmodium, thus with both curative and transmission-blocking activities. The aim of the present work was to investigate whether the class of monovalent ionophores, which includes drugs used in veterinary medicine and that were recently proposed as human anticancer agents, meets these requirements. The activity of salinomycin, monensin, and nigericin on Plasmodium falciparum asexual and sexual erythrocytic stages and on the development of the Plasmodium berghei and P. falciparum mosquito stages is reported here. Gametocytogenesis of the P. falciparum strain 3D7 was induced in vitro, and gametocytes at stage II and III or stage IV and V of development were treated for different lengths of time with the ionophores and their viability measured with the parasite lactate dehydrogenase (pLDH) assay. The monovalent ionophores efficiently killed both asexual parasites and gametocytes with a nanomolar 50% inhibitory concentration (IC50). Salinomycin showed a fast speed of kill compared to that of standard drugs, and the potency was higher on stage IV and V than on stage II and III gametocytes. The ionophores inhibited ookinete development and subsequent oocyst formation in the mosquito midgut, confirming their transmission-blocking activity. Potential toxicity due to hemolysis was excluded, since only infected and not normal erythrocytes were damaged by ionophores. Our data strongly support the downstream exploration of monovalent ionophores for repositioning as new antimalarial and transmission-blocking leads. PMID:26055362

  10. EPIDEMIOLOGICAL AND ENTOMOLOGICAL CORRELATION OF MALARIA TRANSMISSION IN AN AIR FORCE STATION.

    PubMed

    Banerjee, A; Nayak, B

    2001-07-01

    An epidemio-entomological study was carried out at an Air Force Station located in a semi-hilly, forested, highly malarious, tribal belt in Central India. Malaria incidence for the period 1995-1998 showed highest incidence among DSC personnel. Entomological studies identified exophilic vectors (A culicifacies), whose bionomics coincided with outdoor nature of occupation of the DSC personnel. Active surveillance among neighbouring villages showed high endemicity particularly in the tribal villages. Heavy rainfall in 1997 had a slight inhibiting effect on transmission. Because of exophilism of the vectors and occupational hazard of malaria faced by the DSC personnel, personal protective measures hold the key to malaria control in this group.

  11. Transmission blocking effects of neem (Azadirachta indica) seed kernel limonoids on Plasmodium berghei early sporogonic development.

    PubMed

    Tapanelli, Sofia; Chianese, Giuseppina; Lucantoni, Leonardo; Yerbanga, Rakiswendé Serge; Habluetzel, Annette; Taglialatela-Scafati, Orazio

    2016-10-01

    Azadirachta indica, known as neem tree and traditionally called "nature's drug store" makes part of several African pharmacopeias and is widely used for the preparation of homemade remedies and commercial preparations against various illnesses, including malaria. Employing a bio-guided fractionation approach, molecules obtained from A. indica ripe and green fruit kernels were tested for activity against early sporogonic stages of Plasmodium berghei, the parasite stages that develop in the mosquito mid gut after an infective blood meal. The limonoid deacetylnimbin (3) was identified as one the most active compounds of the extract, with a considerably higher activity compared to that of the close analogue nimbin (2). Pure deacetylnimbin (3) appeared to interfere with transmissible Plasmodium stages at a similar potency as azadirachtin A. Considering its higher thermal and chemical stability, deacetylnimbin could represent a suitable alternative to azadirachtin A for the preparation of transmission blocking antimalarials.

  12. Surveillance and Control of Malaria Transmission Using Remotely Sensed Meteorological and Environmental Parameters

    NASA Technical Reports Server (NTRS)

    Kiang, R.; Adimi, F.; Nigro, J.

    2007-01-01

    Meteorological and environmental parameters important to malaria transmission include temperature, relative humidity, precipitation, and vegetation conditions. These parameters can most conveniently be obtained using remote sensing. Selected provinces and districts in Thailand and Indonesia are used to illustrate how remotely sensed meteorological and environmental parameters may enhance the capabilities for malaria surveillance and control. Hindcastings based on these environmental parameters have shown good agreement to epidemiological records.

  13. Unstable, low-level transmission of malaria on the Colombian Pacific Coast.

    PubMed

    González, J M; Olano, V; Vergara, J; Arévalo-Herrera, M; Carrasquilla, G; Herrera, S; López, J A

    1997-06-01

    The development of immune responses to malarial infection in inhabitants of endemic areas differs according to the level of exposure to the parasite. Adults living in a region where the level of malaria transmission is low (Colombia) have been shown to exhibit a similar response to each of the three regions of the circumsporozoite protein (the central repeated NANP region, and the flanking N- and C-termini). Conversely, donors exposed to a frequent sporozoite challenge in areas of high malaria transmission (Mali) exhibit antibodies predominantly to the NANP repeated domain. Malaria in the people of Zacarías, a community on the Pacific Coast of Colombia where malaria transmission is low and unstable, was the subject of the present study. Within a 9-year period, a negative correlation between rainfall and documented malaria cases was recorded for this area. Thick smears of blood samples of 319 individuals revealed that 8.5% had malarial infections. As most (67%) of the smear-positive cases were asymptomatic, it seems that, despite the low prevalence of malaria in this area, the establishment of clinical symptoms is attenuated, probably because of the acquisition of premunition. Within this region, the most commonly found Anopheles species (representing 61.1% of the mosquitoes caught) and that giving the highest monthly biting rate (4.0 bites/man) was An. neivai. Most (90%) of the human sera tested possessed antibodies to blood-stage forms of Plasmodium falciparum, and 18% had antibodies to sporozoites. More than half (58%) of the adults had been in contact with hepatitis B virus, 7.2% carried hepatitis B surface antigen, and syphilis was common but no subject was found to be seropositive for HIV. A better understanding of the dynamics of the different elements influencing malaria in areas of low, unstable transmission, such as the one described here, is essential for the design of new malaria-control strategies.

  14. Surveillance and Control of Malaria Transmission in Thailand using Remotely Sensed Meteorological and Environmental Parameters

    NASA Technical Reports Server (NTRS)

    Kiang, Richard K.; Adimi, Farida; Soika, Valerii; Nigro, Joseph

    2007-01-01

    These slides address the use of remote sensing in a public health application. Specifically, this discussion focuses on the of remote sensing to detect larval habitats to predict current and future endemicity and identify key factors that sustain or promote transmission of malaria in a targeted geographic area (Thailand). In the Malaria Modeling and Surveillance Project, which is part of the NASA Applied Sciences Public Health Applications Program, we have been developing techniques to enhance public health's decision capability for malaria risk assessments and controls. The main objectives are: 1) identification of the potential breeding sites for major vector species; 2) implementation of a risk algorithm to predict the occurrence of malaria and its transmission intensity; 3) implementation of a dynamic transmission model to identify the key factors that sustain or intensify malaria transmission. The potential benefits are: 1) increased warning time for public health organizations to respond to malaria outbreaks; 2) optimized utilization of pesticide and chemoprophylaxis; 3) reduced likelihood of pesticide and drug resistance; and 4) reduced damage to environment. !> Environmental parameters important to malaria transmission include temperature, relative humidity, precipitation, and vegetation conditions. The NASA Earth science data sets that have been used for malaria surveillance and risk assessment include AVHRR Pathfinder, TRMM, MODIS, NSIPP, and SIESIP. Textural-contextual classifications are used to identify small larval habitats. Neural network methods are used to model malaria cases as a function of the remotely sensed parameters. Hindcastings based on these environmental parameters have shown good agreement to epidemiological records. Discrete event simulations are used for modeling the detailed interactions among the vector life cycle, sporogonic cycle and human infection cycle, under the explicit influences of selected extrinsic and intrinsic factors

  15. Malaria transmission in two localities in north-western Argentina

    PubMed Central

    Dantur Juri, María J; Zaidenberg, Mario; Claps, Guillermo L; Santana, Mirta; Almirón, Walter R

    2009-01-01

    Background Malaria is one of the most important tropical diseases that affects people globally. The influence of environmental conditions in the patterns of temporal distribution of malaria vectors and the disease has been studied in different countries. In the present study, ecological aspects of the malaria vector Anopheles (Anopheles) pseudopunctipennis and their relationship with climatic variables, as well as the seasonality of malaria cases, were studied in two localities, El Oculto and Aguas Blancas, in north-western Argentina. Methods The fluctuation of An. pseudopunctipennis and the malaria cases distribution was analysed with Random Effect Poisson Regression. This analysis takes into account the effect of each climatic variable on the abundance of both vector and malaria cases, giving as results predicted values named Incidence Rate Radio. Results The number of specimens collected in El Oculto and Aguas Blancas was 4224 (88.07%) and 572 (11.93%), respectively. In El Oculto no marked seasonality was found, different from Aguas Blancas, where high abundance was detected at the end of spring and the beginning of summer. The maximum mean temperature affected the An. pseudopunctipennis fluctuation in El Oculto and Aguas Blancas. When considering the relationship between the number of malaria cases and the climatic variables in El Oculto, maximum mean temperature and accumulated rainfall were significant, in contrast with Aguas Blancas, where mean temperature and humidity showed a closer relationship to the fluctuation in the disease. Conclusion The temporal distribution patterns of An. pseudopunctipennis vary in both localities, but spring appears as the season with better conditions for mosquito development. Maximum mean temperature was the most important variable in both localities. Malaria cases were influenced by the maximum mean temperature in El Oculto, while the mean temperature and humidity were significant in Aguas Blancas. In Aguas Blancas peaks of

  16. Simulating malaria transmission in the current and future climate of West Africa

    NASA Astrophysics Data System (ADS)

    Yamana, T. K.; Bomblies, A.; Eltahir, E. A. B.

    2015-12-01

    Malaria transmission in West Africa is closely tied to climate, as rain fed water pools provide breeding habitat for the anopheles mosquito vector, and temperature affects the mosquito's ability to spread disease. We present results of a highly detailed, spatially explicit mechanistic modelling study exploring the relationships between the environment and malaria in the current and future climate of West Africa. A mechanistic model of human immunity was incorporated into an existing agent-based model of malaria transmission, allowing us to move beyond entomological measures such as mosquito density and vectorial capacity to analyzing the prevalence of the malaria parasite within human populations. The result is a novel modelling tool that mechanistically simulates all of the key processes linking environment to malaria transmission. Simulations were conducted across climate zones in West Africa, linking temperature and rainfall to entomological and epidemiological variables with a focus on nonlinearities due to threshold effects and interannual variability. Comparisons to observations from the region confirmed that the model provides a reasonable representation of the entomological and epidemiological conditions in this region. We used the predictions of future climate from the most credible CMIP5 climate models to predict the change in frequency and severity of malaria epidemics in West Africa as a result of climate change.

  17. Malaria transmission after five years of vector control on Bioko Island, Equatorial Guinea

    PubMed Central

    2012-01-01

    Background Malaria is endemic with year-round transmission on Bioko Island. The Bioko Island Malaria Control Project (BIMCP) started in 2004 with the aim to reduce malaria transmission and to ultimately eliminate malaria. While the project has been successful in reducing overall malaria morbidity and mortality, foci of high malaria transmission still persist on the island. Results from the 2009 entomological collections are reported here. Methods Human landing collections (HLC) and light trap collections (LTC) were carried out on Bioko Island, Equatorial Guinea in 2009. The HLCs were performed in three locations every second month and LTCs were carried out in 10 locations every second week. Molecular analyses were performed to identify species, detect sporozoites, and identify potential insecticide resistance alleles. Results The entomological inoculation rates (EIR) on Bioko Island ranged from 163 to 840, with the outdoor EIRs reaching > 900 infective mosquito bites per year. All three human landing collection sites on Bioko Island had an annual EIR exceeding the calculated African average of 121 infective bites per year. The highest recorded EIRs were in Punta Europa in northwestern Bioko Island with human biting rates of 92 and 66 mosquito landings per person per night, outdoors and indoors, respectively. Overall, the propensity for mosquito biting on the island was significantly higher outdoors than indoors (p < 0.001). Both Anopheles gambiae s.s. and An. melas were responsible for malaria transmission on the island, but with different geographical distribution patterns. Sporozoite rates were the highest in An. gambiae s.s. populations ranging from 3.1% in Punta Europa and 5.7% in Riaba in the southeast. Only the L1014F (kdr-west) insecticide resistance mutation was detected on the island with frequencies ranging from 22-88% in An. gambiae s.s. No insecticide resistance alleles were detected in the An. melas populations. Conclusions In spite of five years of

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

    PubMed Central

    Wort, Ulrika Uddenfeldt; Hastings, Ian; Mutabingwa, TK; Brabin, Bernard J

    2006-01-01

    Background The impact of malaria on the risk of stillbirth is still under debate. The aim of the present analysis was to determine comparative changes in stillbirth prevalence between two areas of Tanzania with different malaria transmission patterns in order to estimate the malaria attributable component. Methods A retrospective analysis was completed of stillbirth differences between primigravidae and multigravidae in relation to malaria cases and transmission patterns for two different areas of Tanzania with a focus on the effects of the El Niño southern climatic oscillation (ENSO). One area, Kagera, experiences outbreaks of malaria, and the other area, Morogoro, is holoendemic. Delivery and malaria data were collected over a six year period from records of the two district hospitals in these locations. Results There was a significantly higher prevalence of low birthweight in primigravidae compared to multigravidae for both data sets. Low birthweight and stillbirth prevalence (17.5% and 4.8%) were significantly higher in Kilosa compared to Ndolage (11.9% and 2.4%). There was a significant difference in stillbirth prevalence between Ndolage and Kilosa between malaria seasons (2.4% and 5.6% respectively, p < 0.001) and during malaria seasons (1.9% and 5.9% respectively, p < 0.001). During ENSO there was no difference (4.1% and 4.9%, respectively). There was a significant difference in low birthweight prevalence between Ndolage and Kilosa between malaria seasons (14.4% and 23.0% respectively, p < 0.001) and in relation to malaria seasons (13.9% and 25.2% respectively, p < 0.001). During ENSO there was no difference (22.2% and 19.8%, respectively). Increased low birthweight risk occurred approximately five months following peak malaria prevalence, but stillbirth risk increased at the time of malaria peaks. Conclusion Malaria exposure during pregnancy has a delayed effect on birthweight outcomes, but a more acute effect on stillbirth risk. PMID:17044915

  19. Modeling the Effects of Weather and Climate Change on Malaria Transmission

    PubMed Central

    Parham, Paul Edward; Michael, Edwin

    2010-01-01

    Background In recent years, the impact of climate change on human health has attracted considerable attention; the effects on malaria have been of particular interest because of its disease burden and its transmission sensitivity to environmental conditions. Objectives We investigated and illustrated the role that dynamic process-based mathematical models can play in providing strategic insights into the effects of climate change on malaria transmission. Methods We evaluated a relatively simple model that permitted valuable and novel insights into the simultaneous effects of rainfall and temperature on mosquito population dynamics, malaria invasion, persistence and local seasonal extinction, and the impact of seasonality on transmission. We illustrated how large-scale climate simulations and infectious disease systems may be modeled and analyzed and how these methods may be applied to predicting changes in the basic reproduction number of malaria across Tanzania. Results We found extinction to be more strongly dependent on rainfall than on temperature and identified a temperature window of around 32–33°C where endemic transmission and the rate of spread in disease-free regions is optimized. This window was the same for Plasmodium falciparum and P. vivax, but mosquito density played a stronger role in driving the rate of malaria spread than did the Plasmodium species. The results improved our understanding of how temperature shifts affect the global distribution of at-risk regions, as well as how rapidly malaria outbreaks take off within vulnerable populations. Conclusions Disease emergence, extinction, and transmission all depend strongly on climate. Mathematical models offer powerful tools for understanding geographic shifts in incidence as climate changes. Nonlinear dependences of transmission on climate necessitates consideration of both changing climate trends and variability across time scales of interest. PMID:20435552

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

    PubMed

    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.

  1. Mapping Risk of Malaria Transmission in Mainland Portugal Using a Mathematical Modelling Approach

    PubMed Central

    Capinha, César; Rocha, Jorge; Sousa, Carla

    2016-01-01

    Malaria is currently one of the world´s major health problems. About a half-million deaths are recorded every year. In Portugal, malaria cases were significantly high until the end of the 1950s but the disease was considered eliminated in 1973. In the past few years, endemic malaria cases have been recorded in some European countries. With the increasing human mobility from countries with endemic malaria to Portugal, there is concern about the resurgence of this disease in the country. Here, we model and map the risk of malaria transmission for mainland Portugal, considering 3 different scenarios of existing imported infections. This risk assessment resulted from entomological studies on An. atroparvus, the only known mosquito capable of transmitting malaria in the study area. We used the malariogenic potential (determined by receptivity, infectivity and vulnerability) applied over geospatial data sets to estimate spatial variation in malaria risk. The results suggest that the risk exists, and the hotspots are concentrated in the northeast region of the country and in the upper and lower Alentejo regions. PMID:27814371

  2. Mapping Risk of Malaria Transmission in Mainland Portugal Using a Mathematical Modelling Approach.

    PubMed

    Gomes, Eduardo; Capinha, César; Rocha, Jorge; Sousa, Carla

    2016-01-01

    Malaria is currently one of the world´s major health problems. About a half-million deaths are recorded every year. In Portugal, malaria cases were significantly high until the end of the 1950s but the disease was considered eliminated in 1973. In the past few years, endemic malaria cases have been recorded in some European countries. With the increasing human mobility from countries with endemic malaria to Portugal, there is concern about the resurgence of this disease in the country. Here, we model and map the risk of malaria transmission for mainland Portugal, considering 3 different scenarios of existing imported infections. This risk assessment resulted from entomological studies on An. atroparvus, the only known mosquito capable of transmitting malaria in the study area. We used the malariogenic potential (determined by receptivity, infectivity and vulnerability) applied over geospatial data sets to estimate spatial variation in malaria risk. The results suggest that the risk exists, and the hotspots are concentrated in the northeast region of the country and in the upper and lower Alentejo regions.

  3. Dynamics of climate-based malaria transmission model with age-structured human population

    NASA Astrophysics Data System (ADS)

    Addawe, Joel; Pajimola, Aprimelle Kris

    2016-10-01

    In this paper, we proposed to study the dynamics of malaria transmission with periodic birth rate of the vector and an age-structure for the human population. The human population is divided into two compartments: pre-school (0-5 years) and the rest of the human population. We showed the existence of a disease-free equilibrium point. Using published epidemiological parameters, we use numerical simulations to show potential effect of climate change in the dynamics of age-structured malaria transmission. Numerical simulations suggest that there exists an asymptotically attractive solution that is positive and periodic.

  4. Interspecific competition during transmission of two sympatric malaria parasite species to the mosquito vector.

    PubMed Central

    Paul, Rick E L; Nu, Van Anh Ton; Krettli, Antoniana U; Brey, Paul T

    2002-01-01

    The role of species interactions in structuring parasite communities remains controversial. Here, we show that interspecific competition between two avian malaria parasite species, Plasmodium gallinaceum and P. juxtanucleare, occurs as a result of interference during parasite fertilization within the bloodmeal of the mosquito. The significant reduction in the transmission success of P. gallinaceum to mosquitoes, due to the co-infecting P. juxtanucleare, is predicted to have compromised its colonization of regions occupied by P. juxtanucleare and, thus, may have contributed to the restricted global distribution of P. gallinaceum. Such interspecies interactions may occur between human malaria parasites and, thus, impact upon parasite species epidemiology, especially in regions of seasonal transmission. PMID:12573069

  5. Variation in Malaria Transmission Dynamics in Three Different Sites in Western Kenya

    PubMed Central

    Imbahale, S. S.; Mukabana, W. R.; Orindi, B.; Githeko, A. K.; Takken, W.

    2012-01-01

    The main objective was to investigate malaria transmission dynamics in three different sites, two highland villages (Fort Ternan and Lunyerere) and a lowland peri-urban area (Nyalenda) of Kisumu city. Adult mosquitoes were collected using PSC and CDC light trap while malaria parasite incidence data was collected from a cohort of children on monthly basis. Rainfall, humidity and temperature data were collected by automated weather stations. Negative binomial and Poisson generalized additive models were used to examine the risk of being infected, as well as the association with the weather variables. Anopheles gambiae s.s. was most abundant in Lunyerere, An. arabiensis in Nyalenda and An. funestus in Fort Ternan. The CDC light traps caught a higher proportion of mosquitoes (52.3%) than PSC (47.7%), although not significantly different (P = 0.689). The EIR's were 0, 61.79 and 6.91 bites/person/year for Fort Ternan, Lunyerere and Nyalenda. Site, month and core body temperature were all associated with the risk of having malaria parasites (P < 0.0001). Rainfall was found to be significantly associated with the occurrence of P. falciparum malaria parasites, but not relative humidity and air temperature. The presence of malaria parasite-infected children in all the study sites provides evidence of local malaria transmission. PMID:22988466

  6. Malaria-Related Anemia in Patients from Unstable Transmission Areas in Colombia

    PubMed Central

    Lopez-Perez, Mary; Álvarez, Álvaro; Gutierrez, Juan B.; Moreno, Alberto; Herrera, Sócrates; Arévalo-Herrera, Myriam

    2015-01-01

    Information about the prevalence of malarial anemia in areas of low-malaria transmission intensity, like Latin America, is scarce. To characterize the malaria-related anemia, we evaluated 929 malaria patients from three sites in Colombia during 2011–2013. Plasmodium vivax was found to be the most prevalent species in Tierralta (92%), whereas P. falciparum was predominant in Tumaco (84%) and Quibdó (70%). Although severe anemia (hemoglobin < 7 g/dL) was almost absent (0.3%), variable degrees of non-severe anemia were observed in 36.9% of patients. In Tierralta, hemoglobin levels were negatively associated with days of illness. Moreover, in Tierralta and Quibdó, the number of previous malaria episodes and hemoglobin levels were positively associated. Both Plasmodium species seem to have similar potential to induce malarial anemia with distinct cofactors at each endemic setting. The target age in these low-transmission settings seems shifting toward adolescents and young adults. In addition, previous malaria experience seems to induce protection against anemia development. Altogether, these data suggest that early diagnosis and prompt treatment are likely preventing more frequent and serious malaria-related anemia in Colombia. PMID:25510719

  7. Gut microbes influence fitness and malaria transmission potential of Asian malaria vector Anopheles stephensi.

    PubMed

    Sharma, Anil; Dhayal, Devender; Singh, O P; Adak, T; Bhatnagar, Raj K

    2013-10-01

    The midgut of parasite transmitting vector, Anopheles stephensi is a physiologically dynamic ecological niche of resident microbes. The gut resident microbes of anisomorphic and physiologically variable male and female A. stephensi mosquitoes were different (Rani et al., 2009). To understand the possible interaction of gut microbes and mosquito host, we examined the contribution of the microbe community on the fitness of the adult mosquitoes and their ability to permit development of the malaria parasite. A. stephensi mosquitoes were fed with antibiotic to sterilize their gut to study longevity, blood meal digestion, egg laying and maturation capacity, and consequently ability to support malaria parasite development. The sterilization of gut imparted reduction in longevity by a median of 5 days in male and 2 days in female mosquitoes. Similarly, the sterilization also diminished the reproductive potential probably due to increased rate of the resorption of follicles in ovaries coupled with abated blood meal digestion in gut-sterilized females. Additionally, gut sterilization also led to increased susceptibility to oocyst development upon feeding on malaria infected blood. The susceptibility to malaria parasite introduced upon gut sterilization of A. stephensi was restored completely upon re-colonization of gut by native microbes. The information provided in the study provides insights into the role of the gut-resident microbial community in various life events of the mosquito that may be used to develop alternate malaria control strategies, such as paratransgenesis.

  8. Gametocytocidal Screen Identifies Novel Chemical Classes with Plasmodium falciparum Transmission Blocking Activity

    PubMed Central

    Sanders, Natalie G.; Sullivan, David J.; Mlambo, Godfree; Dimopoulos, George; Tripathi, Abhai K.

    2014-01-01

    Discovery of transmission blocking compounds is an important intervention strategy necessary to eliminate and eradicate malaria. To date only a small number of drugs that inhibit gametocyte development and thereby transmission from the mosquito to the human host exist. This limitation is largely due to a lack of screening assays easily adaptable to high throughput because of multiple incubation steps or the requirement for high gametocytemia. Here we report the discovery of new compounds with gametocytocidal activity using a simple and robust SYBR Green I- based DNA assay. Our assay utilizes the exflagellation step in male gametocytes and a background suppressor, which masks the staining of dead cells to achieve healthy signal to noise ratio by increasing signal of viable parasites and subtracting signal from dead parasites. By determining the contribution of exflagellation to fluorescent signal and using appropriate cutoff values, we were able to screen for gametocytocidal compounds. After assay validation and optimization, we screened an FDA approved drug library of approximately 1500 compounds, as well as the 400 compound MMV malaria box and identified 44 gametocytocidal compounds with sub to low micromolar IC50s. Major classes of compounds with gametocytocidal activity included quaternary ammonium compounds with structural similarity to choline, acridine-like compounds similar to quinacrine and pyronaridine, as well as antidepressant, antineoplastic, and anthelminthic compounds. Top drug candidates showed near complete transmission blocking in membrane feeding assays. This assay is simple, reproducible and demonstrated robust Z-factor values at low gametocytemia levels, making it amenable to HTS for identification of novel and potent gametocytocidal compounds. PMID:25157792

  9. Larval nutritional stress affects vector life history traits and human malaria transmission

    PubMed Central

    Vantaux, Amélie; Lefèvre, Thierry; Cohuet, Anna; Dabiré, Kounbobr Roch; Roche, Benjamin; Roux, Olivier

    2016-01-01

    Exposure to stress during an insect’s larval development can have carry-over effects on adult life history traits and susceptibility to pathogens. We investigated the effects of larval nutritional stress for the first time using field mosquito vectors and malaria parasites. In contrast to previous studies, we show that larval nutritional stress may affect human to mosquito transmission antagonistically: nutritionally deprived larvae showed lower parasite prevalence for only one gametocyte carrier; they also had lower fecundity. However, they had greater survival rates that were even higher when infected. When combining these opposing effects into epidemiological models, we show that larval nutritional stress induced a decrease in malaria transmission at low mosquito densities and an increase in transmission at high mosquito densities, whereas transmission by mosquitoes from well-fed larvae was stable. Our work underscores the importance of including environmental stressors towards understanding host–parasite dynamics to improve disease transmission models and control. PMID:27827429

  10. Larval nutritional stress affects vector life history traits and human malaria transmission.

    PubMed

    Vantaux, Amélie; Lefèvre, Thierry; Cohuet, Anna; Dabiré, Kounbobr Roch; Roche, Benjamin; Roux, Olivier

    2016-11-09

    Exposure to stress during an insect's larval development can have carry-over effects on adult life history traits and susceptibility to pathogens. We investigated the effects of larval nutritional stress for the first time using field mosquito vectors and malaria parasites. In contrast to previous studies, we show that larval nutritional stress may affect human to mosquito transmission antagonistically: nutritionally deprived larvae showed lower parasite prevalence for only one gametocyte carrier; they also had lower fecundity. However, they had greater survival rates that were even higher when infected. When combining these opposing effects into epidemiological models, we show that larval nutritional stress induced a decrease in malaria transmission at low mosquito densities and an increase in transmission at high mosquito densities, whereas transmission by mosquitoes from well-fed larvae was stable. Our work underscores the importance of including environmental stressors towards understanding host-parasite dynamics to improve disease transmission models and control.

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

    PubMed

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

    2016-04-01

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

  12. Inhibition of the SR protein-phosphorylating CLK kinases of Plasmodium falciparum impairs blood stage replication and malaria transmission.

    PubMed

    Kern, Selina; Agarwal, Shruti; Huber, Kilian; Gehring, André P; Strödke, Benjamin; Wirth, Christine C; Brügl, Thomas; Abodo, Liliane Onambele; Dandekar, Thomas; Doerig, Christian; Fischer, Rainer; Tobin, Andrew B; Alam, Mahmood M; Bracher, Franz; Pradel, Gabriele

    2014-01-01

    Cyclin-dependent kinase-like kinases (CLKs) are dual specificity protein kinases that phosphorylate Serine/Arginine-rich (SR) proteins involved in pre-mRNA processing. Four CLKs, termed PfCLK-1-4, can be identified in the human malaria parasite Plasmodium falciparum, which show homology with the yeast SR protein kinase Sky1p. The four PfCLKs are present in the nucleus and cytoplasm of the asexual blood stages and of gametocytes, sexual precursor cells crucial for malaria parasite transmission from humans to mosquitoes. We identified three plasmodial SR proteins, PfSRSF12, PfSFRS4 and PfSF-1, which are predominantly present in the nucleus of blood stage trophozoites, PfSRSF12 and PfSF-1 are further detectable in the nucleus of gametocytes. We found that recombinantly expressed SR proteins comprising the Arginine/Serine (RS)-rich domains were phosphorylated by the four PfCLKs in in vitro kinase assays, while a recombinant PfSF-1 peptide lacking the RS-rich domain was not phosphorylated. Since it was hitherto not possible to knock-out the pfclk genes by conventional gene disruption, we aimed at chemical knock-outs for phenotype analysis. We identified five human CLK inhibitors, belonging to the oxo-β-carbolines and aminopyrimidines, as well as the antiseptic chlorhexidine as PfCLK-targeting compounds. The six inhibitors block P. falciparum blood stage replication in the low micromolar to nanomolar range by preventing the trophozoite-to-schizont transformation. In addition, the inhibitors impair gametocyte maturation and gametogenesis in in vitro assays. The combined data show that the four PfCLKs are involved in phosphorylation of SR proteins with essential functions for the blood and sexual stages of the malaria parasite, thus pointing to the kinases as promising targets for antimalarial and transmission blocking drugs.

  13. Malaria

    MedlinePlus

    ... common?Malaria is a health problem in many tropical and subtropical countries, including portions of Central and ... these countries. If you are traveling to a tropical area or to a country where malaria is ...

  14. Border Malaria Associated with Multidrug Resistance on Thailand-Myanmar and Thailand-Cambodia Borders: Transmission Dynamic, Vulnerability, and Surveillance

    PubMed Central

    Bhumiratana, Adisak; Intarapuk, Apiradee; Sorosjinda-Nunthawarasilp, Prapa; Maneekan, Pannamas; Koyadun, Surachart

    2013-01-01

    This systematic review elaborates the concepts and impacts of border malaria, particularly on the emergence and spread of Plasmodium falciparum and Plasmodium vivax multidrug resistance (MDR) malaria on Thailand-Myanmar and Thailand-Cambodia borders. Border malaria encompasses any complex epidemiological settings of forest-related and forest fringe-related malaria, both regularly occurring in certain transmission areas and manifesting a trend of increased incidence in transmission prone areas along these borders, as the result of interconnections of human settlements and movement activities, cross-border population migrations, ecological changes, vector population dynamics, and multidrug resistance. For regional and global perspectives, this review analyzes and synthesizes the rationales pertaining to transmission dynamics and the vulnerabilities of border malaria that constrain surveillance and control of the world's most MDR falciparum and vivax malaria on these chaotic borders. PMID:23865048

  15. Epidemic and Non-Epidemic Hot Spots of Malaria Transmission Occur in Indigenous Comarcas of Panama

    PubMed Central

    Dutari, Larissa C.; Rovira, Jose R.; Sucupira, Izis M. C.; Póvoa, Marinete M.; Conn, Jan E.; Loaiza, Jose R.

    2016-01-01

    From 2002–2005, Panama experienced a malaria epidemic that has been associated with El Niño Southern Oscillation weather patterns, decreased funding for malaria control, and landscape modification. Case numbers quickly decreased afterward, and Panama is now in the pre-elimination stage of malaria eradication. To achieve this new goal, the characterization of epidemiological risk factors, foci of transmission, and important anopheline vectors is needed. Of the 24,681 reported cases in these analyses (2000–2014), ~62% occurred in epidemic years and ~44% in indigenous comarcas (5.9% of Panama’s population). Sub-analyses comparing overall numbers of cases in epidemic and non-epidemic years identified females, comarcas and some 5-year age categories as those disproportionately affected by malaria during epidemic years. Annual parasites indices (APIs; number of cases per 1,000 persons) for Plasmodium vivax were higher in comarcas compared to provinces for all study years, though P. falciparum APIs were only higher in comarcas during epidemic years. Interestingly, two comarcas report increasing numbers of cases annually, despite national annual decreases. Inclusion of these comarcas within identified foci of malaria transmission confirmed their roles in continued transmission. Comparison of species distribution models for two important anophelines with Plasmodium case distribution suggest An. albimanus is the primary malaria vector in Panama, confirmed by identification of nine P. vivax-infected specimen pools. Future malaria eradication strategies in Panama should focus on indigenous comarcas and include both active surveillance for cases and comprehensive anopheline vector surveys. PMID:27182773

  16. Genetic Characterization of Plasmodium Putative Pantothenate Kinase Genes Reveals Their Essential Role in Malaria Parasite Transmission to the Mosquito.

    PubMed

    Hart, Robert J; Cornillot, Emmanuel; Abraham, Amanah; Molina, Emily; Nation, Catherine S; Ben Mamoun, Choukri; Aly, Ahmed S I

    2016-09-20

    The metabolic machinery for the biosynthesis of Coenzyme A (CoA) from exogenous pantothenic acid (Vitamin B5) has long been considered as an excellent target for the development of selective antimicrobials. Earlier studies in the human malaria parasite Plasmodium falciparum have shown that pantothenate analogs interfere with pantothenate phosphorylation and block asexual blood stage development. Although two eukaryotic-type putative pantothenate kinase genes (PanK1 and PanK2) have been identified in all malaria parasite species, their role in the development of Plasmodium life cycle stages remains unknown. Here we report on the genetic characterization of PanK1 and PanK2 in P. yoelii. We show that P. yoelii parasites lacking either PanK1 or PanK2 undergo normal asexual stages development and sexual stages differentiation, however they are severely deficient in ookinete, oocyst and sporozoite formation inside the mosquito vector. Quantitative transcriptional analyses in wild-type and knockout parasites demonstrate an important role for these genes in the regulation of expression of other CoA biosynthesis genes. Together, our data provide the first genetic evidence for the importance of the early steps of pantothenate utilization in the regulation of CoA biosynthesis and malaria parasite transmission to Anopheles mosquitoes.

  17. Genetic Characterization of Plasmodium Putative Pantothenate Kinase Genes Reveals Their Essential Role in Malaria Parasite Transmission to the Mosquito

    PubMed Central

    Hart, Robert J.; Cornillot, Emmanuel; Abraham, Amanah; Molina, Emily; Nation, Catherine S.; Ben Mamoun, Choukri; Aly, Ahmed S. I.

    2016-01-01

    The metabolic machinery for the biosynthesis of Coenzyme A (CoA) from exogenous pantothenic acid (Vitamin B5) has long been considered as an excellent target for the development of selective antimicrobials. Earlier studies in the human malaria parasite Plasmodium falciparum have shown that pantothenate analogs interfere with pantothenate phosphorylation and block asexual blood stage development. Although two eukaryotic-type putative pantothenate kinase genes (PanK1 and PanK2) have been identified in all malaria parasite species, their role in the development of Plasmodium life cycle stages remains unknown. Here we report on the genetic characterization of PanK1 and PanK2 in P. yoelii. We show that P. yoelii parasites lacking either PanK1 or PanK2 undergo normal asexual stages development and sexual stages differentiation, however they are severely deficient in ookinete, oocyst and sporozoite formation inside the mosquito vector. Quantitative transcriptional analyses in wild-type and knockout parasites demonstrate an important role for these genes in the regulation of expression of other CoA biosynthesis genes. Together, our data provide the first genetic evidence for the importance of the early steps of pantothenate utilization in the regulation of CoA biosynthesis and malaria parasite transmission to Anopheles mosquitoes. PMID:27644319

  18. Malaria.

    ERIC Educational Resources Information Center

    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…

  19. Blocking of malaria parasite development in mosquito and fecundity reduction by midgut antibodies in Anopheles stephensi (Diptera: Culicidae).

    PubMed

    Suneja, Amita; Gulia, Monika; Gakhar, S K

    2003-02-01

    Rabbits were immunized three times with extracts of Anopheles stephensi midgut. Immunized rabbits showed a high titer of antibodies when characterized by ELISA. We investigated the effect of anti-mosquito midgut antibodies on mosquito fecundity, longevity, mortality, engorgement, and the development of the malaria parasite in mosquitoes. Fecundity was reduced significantly (38%) and similarly hatchability by about 43.5%. There was no statistically significant effect on mortality, longevity, and engorgement. When the mosquito blood meal contained anti-midgut antibodies, fewer oocysts of Plasmodium vivax developed in the mosquito midgut and the proportion of mosquitoes becoming infected was significantly reduced. We also found that the midgut antibodies inhibit the development and/or translocation of the sporozoites. Antisera raised against midgut of A. stephensi recognized eight polypeptides (110, 92, 70, 45, 38, 29, 15, 13 kDa) by Western blotting. Cross-reactive antigens/epitopes present in other tissues of A. stephensi were also examined both by Western blotting and in vivo ELISA. Together, these observations open an avenue for research toward the development of a vector-based malaria parasite transmission blocking vaccine and/or anti-mosquito vaccine.

  20. Simulation of the Impact of Climate Variability on Malaria Transmission in the Sahel

    NASA Astrophysics Data System (ADS)

    Bomblies, A.; Eltahir, E.; Duchemin, J.

    2007-12-01

    A coupled hydrology and entomology model for simulation of malaria transmission and malaria transmitting mosquito population dynamics is presented. Model development and validation is done using field data and observations collected at Banizoumbou and Zindarou, Niger spanning three wet seasons, from 2005 through 2007. The primary model objective is the accurate determination of climate variability effects on village scale malaria transmission. Malaria transmission dependence on climate variables is highly nonlinear and complex. Temperature and humidity affect mosquito longevity, temperature controls parasite development rates in the mosquito as well as subadult mosquito development rates, and precipitation determines the formation and persistence of adequate breeding pools. Moreover, unsaturated zone hydrology influences overland flow, and climate controlled evapotranspiration rates and root zone uptake therefore also influence breeding pool formation. High resolution distributed hydrologic simulation allows representation of the small-scale ephemeral pools that constitute the primary habitat of Anopheles gambiae mosquitoes, the dominant malaria vectors in the Niger Sahel. Remotely sensed soil type, vegetation type, and microtopography rasters are used to assign the distributed parameter fields for simulation of the land surface hydrologic response to precipitation and runoff generation. Predicted runoff from each cell flows overland and into topographic depressions, with explicit representation of infiltration and evapotranspiration. The model's entomology component interacts with simulated pools. Subadult (aquatic stage) mosquito breeding is simulated in the pools, and water temperature dependent stage advancement rates regulate adult mosquito emergence into the model domain. Once emerged, adult mosquitoes are tracked as independent individual agents that interact with their immediate environment. Attributes relevant to malaria transmission such as gonotrophic

  1. Linking environmental variability to village-scale malaria transmission using a simple immunity model

    PubMed Central

    2013-01-01

    Background Individuals continuously exposed to malaria gradually acquire immunity that protects from severe disease and high levels of parasitization. Acquired immunity has been incorporated into numerous models of malaria transmission of varying levels of complexity (e.g. Bull World Health Organ 50:347, 1974; Am J Trop Med Hyg 75:19, 2006; Math Biosci 90:385–396, 1988). Most such models require prescribing inputs of mosquito biting rates or other entomological or epidemiological information. Here, we present a model with a novel structure that uses environmental controls of mosquito population dynamics to simulate the mosquito biting rates, malaria prevalence as well as variability in protective immunity of the population. Methods A simple model of acquired immunity to malaria is presented and tested within the framework of the Hydrology, Entomology and Malaria Transmission Simulator (HYDREMATS), a coupled hydrology and agent-based entomology model. The combined model uses environmental data including rainfall, temperature, and topography to simulate malaria prevalence and level of acquired immunity in the human population. The model is used to demonstrate the effect of acquired immunity on malaria prevalence in two Niger villages that are hydrologically and entomologically very different. Simulations are conducted for the year 2006 and compared to malaria prevalence observations collected from the two villages. Results Blood smear samples from children show no clear difference in malaria prevalence between the two villages despite pronounced differences in observed mosquito abundance. The similarity in prevalence is attributed to the moderating effect of acquired immunity, which depends on prior exposure to the parasite through infectious bites - and thus the hydrologically determined mosquito abundance. Modelling the level of acquired immunity can affect village vulnerability to climatic anomalies. Conclusions The model presented has a novel structure

  2. A simple pond parametrization for malaria transmission models

    NASA Astrophysics Data System (ADS)

    Tompkins, A. M.; Asare, E.; Amekudzi, L. K.

    2012-04-01

    In order to model malaria effectively using a dynamical modelling approach, a realistic representation of the surface hydrology is required. Achieving this goal is hindered by the fact that key vector breeding sites are small in spatial scale, ranging from small permanent ponds to temporary puddles. This small spatial scale confounds modelling efforts as the topography on such small scales is unknown, and also renders detection by remote sensing techniques difficult implying a requirement of in-situ measurements. Results from ongoing measurements of breeding sites in Kumasi (Ghana) are shown, along with attempts to reproduce these using a simple pond 'parametrization'. The significant impact of the pond model implementation and settings on malaria simulations using the new VECTRI dynamical disease model is demonstrated.

  3. Epidemiologic aspects of the malaria transmission cycle in an area of very low incidence in Brazil

    PubMed Central

    Cerutti, Crispim; Boulos, Marcos; Coutinho, Arnídio F; Hatab, Maria do Carmo LD; Falqueto, Aloísio; Rezende, Helder R; Duarte, Ana Maria RC; Collins, William; Malafronte, Rosely S

    2007-01-01

    "classical" P. vivax (VK210), VK247, P. vivax-like and P. malariae, respectively. Anopheline captures in the transmission area revealed only zoophilic and exophilic species. Conclusion The low incidence of malaria cases, the finding of asymptomatic inhabitants and the geographic separation of patients allied to serological and molecular results raise the possibility of the existence of a simian reservoir in these areas. PMID:17371598

  4. Immune response and insulin signalling alter mosquito feeding behaviour to enhance malaria transmission potential

    PubMed Central

    Cator, Lauren J.; Pietri, Jose E.; Murdock, Courtney C.; Ohm, Johanna R.; Lewis, Edwin E.; Read, Andrew F.; Luckhart, Shirley; Thomas, Matthew B.

    2015-01-01

    Malaria parasites alter mosquito feeding behaviour in a way that enhances parasite transmission. This is widely considered a prime example of manipulation of host behaviour to increase onward transmission, but transient immune challenge in the absence of parasites can induce the same behavioural phenotype. Here, we show that alterations in feeding behaviour depend on the timing and dose of immune challenge relative to blood ingestion and that these changes are functionally linked to changes in insulin signalling in the mosquito gut. These results suggest that altered phenotypes derive from insulin signalling-dependent host resource allocation among immunity, blood feeding, and reproduction in a manner that is not specific to malaria parasite infection. We measured large increases in mosquito survival and subsequent transmission potential when feeding patterns are altered. Leveraging these changes in physiology, behaviour and life history could promote effective and sustainable control of female mosquitoes responsible for transmission. PMID:26153094

  5. Immune response and insulin signalling alter mosquito feeding behaviour to enhance malaria transmission potential.

    PubMed

    Cator, Lauren J; Pietri, Jose E; Murdock, Courtney C; Ohm, Johanna R; Lewis, Edwin E; Read, Andrew F; Luckhart, Shirley; Thomas, Matthew B

    2015-07-08

    Malaria parasites alter mosquito feeding behaviour in a way that enhances parasite transmission. This is widely considered a prime example of manipulation of host behaviour to increase onward transmission, but transient immune challenge in the absence of parasites can induce the same behavioural phenotype. Here, we show that alterations in feeding behaviour depend on the timing and dose of immune challenge relative to blood ingestion and that these changes are functionally linked to changes in insulin signalling in the mosquito gut. These results suggest that altered phenotypes derive from insulin signalling-dependent host resource allocation among immunity, blood feeding, and reproduction in a manner that is not specific to malaria parasite infection. We measured large increases in mosquito survival and subsequent transmission potential when feeding patterns are altered. Leveraging these changes in physiology, behaviour and life history could promote effective and sustainable control of female mosquitoes responsible for transmission.

  6. The dynamics, transmission, and population impacts of avian malaria in native hawaiian birds: A modeling approach

    USGS Publications Warehouse

    Samuel, M.D.; Hobbelen, P.H.F.; Decastro, F.; Ahumada, J.A.; Lapointe, D.A.; Atkinson, C.T.; Woodworth, B.L.; Hart, P.J.; Duffy, D.C.

    2011-01-01

    We developed an epidemiological model of avian malaria (Plasmodium relictum) across an altitudinal gradient on the island of Hawaii that includes the dynamics of the host, vector, and parasite. This introduced mosquito-borne disease is hypothesized to have contributed to extinctions and major shifts in the altitudinal distribution of highly susceptible native forest birds. Our goal was to better understand how biotic and abiotic factors influence the intensity of malaria transmission and impact on susceptible populations of native Hawaiian forest birds. Our model illustrates key patterns in the malaria-forest bird system: high malaria transmission in low-elevation forests with minor seasonal or annual variation in infection;episodic transmission in mid-elevation forests with site-to-site, seasonal, and annual variation depending on mosquito dynamics;and disease refugia in high-elevation forests with only slight risk of infection during summer. These infection patterns are driven by temperature and rainfall effects on parasite incubation period and mosquito dynamics across an elevational gradient and the availability of larval habitat, especially in mid-elevation forests. The results from our model suggest that disease is likely a key factor in causing population decline or restricting the distribution of many susceptible Hawaiian species and preventing the recovery of other vulnerable species. The model also provides a framework for the evaluation of factors influencing disease transmission and alternative disease control programs, and to evaluate the impact of climate change on disease cycles and bird populations. ??2011 by the Ecological Society of America.

  7. Malaria

    PubMed Central

    Suh, Kathryn N.; Kain, Kevin C.; Keystone, Jay S.

    2004-01-01

    Malaria is a parasitic infection of global importance. Although relatively uncommon in developed countries, where the disease occurs mainly in travellers who have returned from endemic regions, it remains one of the most prevalent infections of humans worldwide. In endemic regions, malaria is a significant cause of morbidity and mortality and creates enormous social and economic burdens. Current efforts to control malaria focus on reducing attributable morbidity and mortality. Targeted chemoprophylaxis and use of insecticide-treated bed nets have been successful in some endemic areas. For travellers to malaria-endemic regions, personal protective measures and appropriate chemoprophylaxis can significantly reduce the risk of infection. Prompt evaluation of the febrile traveller, a high degree of suspicion of malaria, rapid and accurate diagnosis, and appropriate antimalarial therapy are essential in order to optimize clinical outcomes of infected patients. Additional approaches to malaria control, including genetic manipulation of mosquitoes and malaria vaccines, are areas of ongoing research. PMID:15159369

  8. A New Set of Chemical Starting Points with Plasmodium falciparum Transmission-Blocking Potential for Antimalarial Drug Discovery

    PubMed Central

    Almela, Maria Jesus; Lozano, Sonia; Lelièvre, Joël; Colmenarejo, Gonzalo; Coterón, José Miguel; Rodrigues, Janneth; Gonzalez, Carolina; Herreros, Esperanza

    2015-01-01

    The discovery of new antimalarials with transmission blocking activity remains a key issue in efforts to control malaria and eventually eradicate the disease. Recently, high-throughput screening (HTS) assays have been successfully applied to Plasmodium falciparum asexual stages to screen millions of compounds, with the identification of thousands of new active molecules, some of which are already in clinical phases. The same approach has now been applied to identify compounds that are active against P. falciparum gametocytes, the parasite stage responsible for transmission. This study reports screening results for the Tres Cantos Antimalarial Set (TCAMS), of approximately 13,533 molecules, against P. falciparum stage V gametocytes. Secondary confirmation and cytotoxicity assays led to the identification of 98 selective molecules with dual activity against gametocytes and asexual stages. Hit compounds were chemically clustered and analyzed for appropriate physicochemical properties. The TCAMS chemical space around the prioritized hits was also studied. A selection of hit compounds was assessed ex vivo in the standard membrane feeding assay and demonstrated complete block in transmission. As a result of this effort, new chemical structures not connected to previously described antimalarials have been identified. This new set of compounds may serve as starting points for future drug discovery programs as well as tool compounds for identifying new modes of action involved in malaria transmission. PMID:26317851

  9. Transmission blocking activity of Azadirachta indica and Guiera senegalensis extracts on the sporogonic development of Plasmodium falciparum field isolates in Anopheles coluzzii mosquitoes

    PubMed Central

    2014-01-01

    Background Targeting the stages of the malaria parasites responsible for transmission from the human host to the mosquito vector is a key pharmacological strategy for malaria control. Research efforts to identify compounds that are active against these stages have significantly increased in recent years. However, at present, only two drugs are available, namely primaquine and artesunate, which reportedly act on late stage gametocytes. Methods In this study, we assessed the antiplasmodial effects of 5 extracts obtained from the neem tree Azadirachta indica and Guiera senegalensis against the early vector stages of Plasmodium falciparum, using field isolates. In an ex vivo assay gametocytaemic blood was supplemented with the plant extracts and offered to Anopheles coluzzii females by membrane feeding. Transmission blocking activity was evaluated by assessing oocyst prevalence and density on the mosquito midguts. Results Initial screening of the 5 plant extracts at 250 ppm revealed transmission blocking activity in two neem preparations. Up to a concentration of 70 ppm the commercial extract NeemAzal® completely blocked transmission and at 60 ppm mosquitoes of 4 out of 5 replicate groups remained uninfected. Mosquitoes fed on the ethyl acetate phase of neem leaves at 250 ppm showed a reduction in oocyst prevalence of 59.0% (CI95 12.0 - 79.0; p < 10-4) and in oocyst density of 90.5% (CI95 86.0 - 93.5; p < 10-4 ), while the ethanol extract from the same plant part did not exhibit any activity. No evidence of transmission blocking activity was found using G. senegalensis ethyl acetate extract from stem galls. Conclusions The results of this study highlight the potential of antimalarial plants for the discovery of novel transmission blocking molecules, and open up the potential of developing standardized transmission blocking herbal formulations as malaria control tools to complement currently used antimalarial drugs and combination treatments. PMID:24735564

  10. Hotspots of Malaria Transmission in the Peruvian Amazon: Rapid Assessment through a Parasitological and Serological Survey

    PubMed Central

    Rosas-Aguirre, Angel; Speybroeck, Niko; Llanos-Cuentas, Alejandro; Rosanas-Urgell, Anna; Carrasco-Escobar, Gabriel; Rodriguez, Hugo; Gamboa, Dionicia; Contreras-Mancilla, Juan; Alava, Freddy; Soares, Irene S.; Remarque, Edmond; D´Alessandro, Umberto; Erhart, Annette

    2015-01-01

    Background With low and markedly seasonal malaria transmission, increasingly sensitive tools for better stratifying the risk of infection and targeting control interventions are needed. A cross-sectional survey to characterize the current malaria transmission patterns, identify hotspots, and detect recent changes using parasitological and serological measures was conducted in three sites of the Peruvian Amazon. Material and Methods After full census of the study population, 651 participants were interviewed, clinically examined and had a blood sample taken for the detection of malaria parasites (microscopy and PCR) and antibodies against P. vivax (PvMSP119, PvAMA1) and P. falciparum (PfGLURP, PfAMA1) antigens by ELISA. Risk factors for malaria infection (positive PCR) and malaria exposure (seropositivity) were assessed by multivariate survey logistic regression models. Age-specific seroprevalence was analyzed using a reversible catalytic conversion model based on maximum likelihood for generating seroconversion rates (SCR, λ). SaTScan was used to detect spatial clusters of serology-positive individuals within each site. Results The overall parasite prevalence by PCR was low, i.e. 3.9% for P. vivax and 6.7% for P. falciparum, while the seroprevalence was substantially higher, 33.6% for P. vivax and 22.0% for P. falciparum, with major differences between study sites. Age and location (site) were significantly associated with P. vivax exposure; while location, age and outdoor occupation were associated with P. falciparum exposure. P. falciparum seroprevalence curves showed a stable transmission throughout time, while for P. vivax transmission was better described by a model with two SCRs. The spatial analysis identified well-defined clusters of P. falciparum seropositive individuals in two sites, while it detected only a very small cluster of P. vivax exposure. Conclusion The use of a single parasitological and serological malaria survey has proven to be an efficient

  11. Intricacies of using temperature of different niches for assessing impact on malaria transmission

    PubMed Central

    Singh, Poonam; Yadav, Yogesh; Saraswat, Shweta; Dhiman, Ramesh C.

    2016-01-01

    Background & objectives: The influence of temperature on the life cycle of mosquitoes as well as on development of malaria parasite in mosquitoes is well studied. Most of the studies use outdoor temperature for understanding the transmission dynamics and providing projections of malaria. As the mosquitoes breed in water and rest usually indoors, it is logical to relate the transmission dynamics with temperature of micro-niche. The present study was, therefore, undertaken to understand the influence of different formats of temperature of different micro-niches on transmission of malaria for providing more realistic projections. Methods: The study was conducted in one village each of Assam and Uttarakhand States of India. Temperatures recorded from outdoor (air) as well as indoor habitats (resting place of mosquito) were averaged into daily, fortnightly and monthly and were used for determination of transmission windows (TWs) for Plasmodium vivax (Pv) and P. falciparum (Pf) based on minimum temperature threshold required for transmission. Results: The daily temperature was found more useful for calculation of sporogony than fortnightly and monthly temperatures. Monthly TWs were further refined using fortnightly temperature, keeping in view the completion of more than one life cycle of malaria vectors and sporogony of malaria parasite in a month. A linear regression equation was generated to find out the relationship between outdoor and indoor temperatures and R2 to predict the percentage of variation in indoor temperature as a function of outdoor temperature at both localities. Interpretation & conclusions: The study revealed that the indoor temperature was more than outdoors in stable malarious area (Assam) but fluctuating in low endemic area like Uttarakhand. Transmission windows of malaria should be determined by transforming outdoor data to indoor and preferably at fortnightly interval. With daily recorded temperature, sporogonic and gonotrophic cycles can also

  12. Survey for asymptomatic malaria cases in low transmission settings of Iran under elimination programme

    PubMed Central

    2012-01-01

    Background In malaria endemic areas, continuous exposure to Plasmodium parasites leads to asymptomatic carriers that provide a fundamental reservoir of parasites, contributing to the persistence of malaria transmission. Therefore, in the present investigation, the presence and prevalence of malaria asymptomatic cases were determined to evaluate the reservoir of infection in two malaria endemic areas with a previous history of malaria transmission in the south of Iran, Bashagard and Ghale-Ganj districts of Hormozgan and Kerman provinces, respectively, where malaria transmission has been drastically reduced in the recent years. Methods The population samples (n=500 from each of the studied areas) were randomly collected from non-febrile, long-term residing, aged two to over 60years, during 20092010. Three identical surveys were carried out in both study areas and in each phase all the consent participants were interviewed and clinically examined. In all, three surveys to detect hidden parasite reservoirs (both Plasmodium falciparum and Plasmodium vivax), thick and thin blood smears and a highly sensitive nested-PCR were applied. In addition, the sero-prevalence survey for detecting malaria exposure was done by using a serological marker. Results In this study, P. vivax and P. falciparum parasites were not detected by light microscopy and nested-PCR assay in all three surveys of samples. Antibody responses against P. vivax and P. falciparum were detected in 1 % and 0.2 % of the total examined individuals, respectively, in Bashagard district. Regarding to Ghale-Ganj district, about 0.9% of the individuals had IgG -specific antibody to P. vivax at the first and second surveys, but at the third survey 0.45% of the participants had positive antibody to P. vivax parasite. IgG -specific antibody to P. falciparum was detected in 0.2% of the participants at the first and follow-up surveys. The overall regional differences were not statistically significant (P>0

  13. Transmission block to simplify combined pelvic and inguinal radiation therapy.

    PubMed

    Kalnicki, S; Zide, A; Maleki, N; DeWyngaert, J K; Lipsztein, R; Dalton, J F; Bloomer, W D

    1987-08-01

    A homogeneous dose distribution of radiation to inguinal lymph nodes and deep pelvic structures can be achieved with use of a transmission block over the central portion of a large anterior pelvic-inguinal portal, together with a smaller posterior field. This relatively simple technique permits individualization of isodose distributions and eliminates the problems of matching abutting portals. Reproducibility of daily setup and optimization of machine utilization are both improved.

  14. Remote Sensing-Driven Climatic/Environmental Variables for Modelling Malaria Transmission in Sub-Saharan Africa

    PubMed Central

    Ebhuoma, Osadolor; Gebreslasie, Michael

    2016-01-01

    Malaria is a serious public health threat in Sub-Saharan Africa (SSA), and its transmission risk varies geographically. Modelling its geographic characteristics is essential for identifying the spatial and temporal risk of malaria transmission. Remote sensing (RS) has been serving as an important tool in providing and assessing a variety of potential climatic/environmental malaria transmission variables in diverse areas. This review focuses on the utilization of RS-driven climatic/environmental variables in determining malaria transmission in SSA. A systematic search on Google Scholar and the Institute for Scientific Information (ISI) Web of KnowledgeSM databases (PubMed, Web of Science and ScienceDirect) was carried out. We identified thirty-five peer-reviewed articles that studied the relationship between remotely-sensed climatic variable(s) and malaria epidemiological data in the SSA sub-regions. The relationship between malaria disease and different climatic/environmental proxies was examined using different statistical methods. Across the SSA sub-region, the normalized difference vegetation index (NDVI) derived from either the National Oceanic and Atmospheric Administration (NOAA) Advanced Very High Resolution Radiometer (AVHRR) or Moderate-resolution Imaging Spectrometer (MODIS) satellite sensors was most frequently returned as a statistically-significant variable to model both spatial and temporal malaria transmission. Furthermore, generalized linear models (linear regression, logistic regression and Poisson regression) were the most frequently-employed methods of statistical analysis in determining malaria transmission predictors in East, Southern and West Africa. By contrast, multivariate analysis was used in Central Africa. We stress that the utilization of RS in determining reliable malaria transmission predictors and climatic/environmental monitoring variables would require a tailored approach that will have cognizance of the geographical

  15. Remote Sensing-Driven Climatic/Environmental Variables for Modelling Malaria Transmission in Sub-Saharan Africa.

    PubMed

    Ebhuoma, Osadolor; Gebreslasie, Michael

    2016-06-14

    Malaria is a serious public health threat in Sub-Saharan Africa (SSA), and its transmission risk varies geographically. Modelling its geographic characteristics is essential for identifying the spatial and temporal risk of malaria transmission. Remote sensing (RS) has been serving as an important tool in providing and assessing a variety of potential climatic/environmental malaria transmission variables in diverse areas. This review focuses on the utilization of RS-driven climatic/environmental variables in determining malaria transmission in SSA. A systematic search on Google Scholar and the Institute for Scientific Information (ISI) Web of Knowledge(SM) databases (PubMed, Web of Science and ScienceDirect) was carried out. We identified thirty-five peer-reviewed articles that studied the relationship between remotely-sensed climatic variable(s) and malaria epidemiological data in the SSA sub-regions. The relationship between malaria disease and different climatic/environmental proxies was examined using different statistical methods. Across the SSA sub-region, the normalized difference vegetation index (NDVI) derived from either the National Oceanic and Atmospheric Administration (NOAA) Advanced Very High Resolution Radiometer (AVHRR) or Moderate-resolution Imaging Spectrometer (MODIS) satellite sensors was most frequently returned as a statistically-significant variable to model both spatial and temporal malaria transmission. Furthermore, generalized linear models (linear regression, logistic regression and Poisson regression) were the most frequently-employed methods of statistical analysis in determining malaria transmission predictors in East, Southern and West Africa. By contrast, multivariate analysis was used in Central Africa. We stress that the utilization of RS in determining reliable malaria transmission predictors and climatic/environmental monitoring variables would require a tailored approach that will have cognizance of the geographical

  16. Transmission-blocking strategies: the roadmap from laboratory bench to the community.

    PubMed

    Gonçalves, Daniel; Hunziker, Patrick

    2016-02-18

    Malaria remains one of the most prevalent tropical and infectious diseases in the world, with an estimated more than 200 million clinical cases every year. In recent years, the mosquito stages of the parasite life cycle have received renewed attention with some progress being made in the development of transmission-blocking strategies. From gametocytes to late ookinetes, some attractive antigenic targets have been found and tested in order to develop a transmission blocking vaccine, and drugs are being currently screened for gametocytocidal activity, and also some new and less conventional approaches are drawing increased attention, such as genetically modified and fungus-infected mosquitoes that become refractory to Plasmodium infection. In this review some of those strategies focusing on the progress made so far will be summarized, but also, the challenges that come from the translation of early promising benchwork resulting in successful applications in the field. To do this, the available literature will be screened and all the pieces of the puzzle must be combined: from molecular biology to epidemiologic and clinical data.

  17. Delayed mortality effects cut the malaria transmission potential of insecticide-resistant mosquitoes

    PubMed Central

    Viana, Mafalda; Hughes, Angela; Matthiopoulos, Jason; Ranson, Hilary; Ferguson, Heather M.

    2016-01-01

    Malaria transmission has been substantially reduced across Africa through the distribution of long-lasting insecticidal nets (LLINs). However, the emergence of insecticide resistance within mosquito vectors risks jeopardizing the future efficacy of this control strategy. The severity of this threat is uncertain because the consequences of resistance for mosquito fitness are poorly understood: while resistant mosquitoes are no longer immediately killed upon contact with LLINs, their transmission potential may be curtailed because of longer-term fitness costs that persist beyond the first 24 h after exposure. Here, we used a Bayesian state-space model to quantify the immediate (within 24 h of exposure) and delayed (>24 h after exposure) impact of insecticides on daily survival and malaria transmission potential of moderately and highly resistant laboratory populations of the major African malaria vector Anopheles gambiae. Contact with LLINs reduced the immediate survival of moderately and highly resistant An. gambiae strains by 60–100% and 3–61%, respectively, and delayed mortality impacts occurring beyond the first 24 h after exposure further reduced their overall life spans by nearly one-half. In total, insecticide exposure was predicted to reduce the lifetime malaria transmission potential of insecticide-resistant vectors by two-thirds, with delayed effects accounting for at least one-half of this reduction. The existence of substantial, previously unreported, delayed mortality effects within highly resistant malaria vectors following exposure to insecticides does not diminish the threat of growing resistance, but posits an explanation for the apparent paradox of continued LLIN effectiveness in the presence of high insecticide resistance. PMID:27402740

  18. Modest additive effects of integrated vector control measures on malaria prevalence and transmission in western Kenya

    PubMed Central

    2013-01-01

    Background The effect of integrating vector larval intervention on malaria transmission is unknown when insecticide-treated bed-net (ITN) coverage is very high, and the optimal indicator for intervention evaluation needs to be determined when transmission is low. Methods A post hoc assignment of intervention-control cluster design was used to assess the added effect of both indoor residual spraying (IRS) and Bacillus-based larvicides (Bti) in addition to ITN in the western Kenyan highlands in 2010 and 2011. Cross-sectional, mass parasite screenings, adult vector populations, and cohort of active case surveillance (ACS) were conducted before and after the intervention in three study sites with two- to three-paired intervention-control clusters at each site each year. The effect of larviciding, IRS, ITNs and other determinants of malaria risk was assessed by means of mixed estimating methods. Results Average ITN coverage increased from 41% in 2010 to 92% in 2011 in the study sites. IRS intervention had significant added impact on reducing vector density in 2010 but the impact was modest in 2011. The effect of IRS on reducing parasite prevalence was significant in 2011 but was seasonal specific in 2010. ITN was significantly associated with parasite densities in 2010 but IRS application was significantly correlated with reduced gametocyte density in 2011. IRS application reduced about half of the clinical malaria cases in 2010 and about one-third in 2011 compare to non-intervention areas. Conclusion Compared with a similar study conducted in 2005, the efficacy of the current integrated vector control with ITN, IRS, and Bti reduced three- to five-fold despite high ITN coverage, reflecting a modest added impact on malaria transmission. Additional strategies need to be developed to further reduce malaria transmission. PMID:23870708

  19. Dynamics of Forest Malaria Transmission in Balaghat District, Madhya Pradesh, India

    PubMed Central

    Singh, Neeru; Chand, Sunil K.; Bharti, Praveen K.; Singh, Mrigendra P.; Chand, Gyan; Mishra, Ashok K.; Shukla, Man M.; Mahulia, Man M.; Sharma, Ravendra K.

    2013-01-01

    Background An epidemiological and entomological study was carried out in Balaghat district, Madhya Pradesh, India to understand the dynamics of forest malaria transmission in a difficult and hard to reach area where indoor residual spray and insecticide treated nets were used for vector control. Methods This community based cross-sectional study was undertaken from January 2010 to December 2012 in Baihar and Birsa Community Health Centres of district Balaghat for screening malaria cases. Entomological surveillance included indoor resting collections, pyrethrum spray catches and light trap catches. Anophelines were assayed by ELISA for detection of Plasmodium circumsporozoite protein. Findings Plasmodium falciparum infection accounted for >80% of all infections. P. vivax 16.5%, P. malariae 0.75% and remaining were mixed infections of P. falciparum, P. vivax and P. malariae. More than, 30% infections were found in infants under 6 months of age. Overall, an increasing trend in malaria positivity was observed from 2010 to 2012 (chi-square for trend  =  663.55; P<0.0001). Twenty five Anopheles culicifacies (sibling species C, D and E) were positive for circumsporozoite protein of P. falciparum (44%) and P. vivax (56%). Additionally, 2 An. fluviatilis, were found positive for P. falciparum and 1 for P. vivax (sibling species S and T). An. fluviatilis sibling species T was found as vector in forest villages for the first time in India. Conclusion These results showed that the study villages are experiencing almost perennial malaria transmission inspite of indoor residual spray and insecticide treated nets. Therefore, there is a need for new indoor residual insecticides which has longer residual life or complete coverage of population with long lasting insecticide treated nets or both indoor residual spray and long lasting bed nets for effective vector control. There is a need to undertake a well designed case control study to evaluate the efficacy of these

  20. Utilizing direct skin feeding assays for development of vaccines that interrupt malaria transmission: A systematic review of methods and case study.

    PubMed

    Brickley, Elizabeth B; Coulibaly, Mamadou; Gabriel, Erin E; Healy, Sara A; Hume, Jen C C; Sagara, Issaka; Traore, Sekou F; Doumbo, Ogobara; Duffy, Patrick E

    2016-11-21

    Shifting the malaria priorities from a paradigm of control and elimination to a goal of global eradication calls for renewed attention to the interruption of malaria transmission. Sustained progress toward eradication will require both improved understanding of infectious reservoirs and efficient development of novel transmission-blocking interventions, such as rapidly acting and highly efficacious therapeutics and vaccines. Here, we review the direct skin feeding assay (DSF), which has been proposed as a valuable tool for measuring the in natura transmission of malaria parasites from human hosts to mosquito vectors across heterogeneous populations. To capture the methodological breadth of this assay's use, we first systematically review and qualitatively synthesize previously published investigations using DSFs to study malaria transmission in humans. Then, using a recent Phase 1 trial in Mali of the Pfs25H-EPA/Alhydrogel® vaccine candidate (NCT01867463) designed to interrupt Plasmodium falciparum transmission as a case study, we describe the potential opportunities and current limitations of utilizing the endpoints measured by DSF in making early clinical decisions for individually randomized transmission-interrupting intervention candidates. Using simulations based on the data collected in the clinical trial, we demonstrate that the capacity of the DSF to serve as an evaluative tool is limited by the statistical power constraints of the "effective sample size" (i.e. the number of subjects that are capable of transmitting at the time of feeding). Altogether, our findings suggest DSFs have great potential utility for assessing the public health impacts of emerging antimalarial tools, but additional research is needed to address issues of scalability and to establish correlation with community-wide clinical endpoints as well as complementary in vitro measures, such as standard membrane feeding assays.

  1. Epidemiology of malaria in an area of seasonal transmission in Niger and implications for the design of a seasonal malaria chemoprevention strategy

    PubMed Central

    2013-01-01

    Background Few data are available about malaria epidemiological situation in Niger. However, implementation of new strategies such as vaccination or seasonal treatment of a target population requires the knowledge of baseline epidemiological features of malaria. A population-based study was conducted to provide better characterization of malaria seasonal variations and population groups the most at risk in this particular area. Methods From July 2007 to December 2009, presumptive cases of malaria among a study population living in a typical Sahelian village of Niger were recorded, and confirmed by microscopic examination. In parallel, asymptomatic carriers were actively detected at the end of each dry season in 2007, 2008 and 2009. Results Among the 965 presumptive malaria cases recorded, 29% were confirmed by microscopic examination. The incidence of malaria was found to decrease significantly with age (p < 0.01). The mean annual incidence was 0.254. The results show that the risk of malaria was higher in children under ten years (p < 0.0001). The number of malaria episodes generally followed the temporal pattern of changes in precipitation levels, with a peak of transmission in August and September. One-thousand and ninety subjects were submitted to an active detection of asymptomatic carriage of whom 16% tested positive; asymptomatic carriage decreased with increasing age. A higher prevalence of gametocyte carriage among asymptomatic population was recorded in children aged two to ten years, though it did not reach significance. Conclusions In Southern Niger, malaria transmission mostly occurs from July to October. Children aged two to ten years are the most at risk of malaria, and may also represent the main reservoir for gametocytes. Strategies such as intermittent preventive treatment in children (IPTc) could be of interest in this area, where malaria transmission is highly seasonal. Based on these preliminary data, a pilot study could be implemented

  2. A vectorial capacity product to monitor changing malaria transmission potential in epidemic regions of Africa

    USGS Publications Warehouse

    Ceccato, Pietro; Vancutsem, Christelle; Klaver, Robert; Rowland, James; Connor, Stephen J.

    2012-01-01

    Rainfall and temperature are two of the major factors triggering malaria epidemics in warm semi-arid (desert-fringe) and high altitude (highland-fringe) epidemic risk areas. The ability of the mosquitoes to transmit Plasmodium spp. is dependent upon a series of biological features generally referred to as vectorial capacity. In this study, the vectorial capacity model (VCAP) was expanded to include the influence of rainfall and temperature variables on malaria transmission potential. Data from two remote sensing products were used to monitor rainfall and temperature and were integrated into the VCAP model. The expanded model was tested in Eritrea and Madagascar to check the viability of the approach. The analysis of VCAP in relation to rainfall, temperature and malaria incidence data in these regions shows that the expanded VCAP correctly tracks the risk of malaria both in regions where rainfall is the limiting factor and in regions where temperature is the limiting factor. The VCAP maps are currently offered as an experimental resource for testing within Malaria Early Warning applications in epidemic prone regions of sub-Saharan Africa. User feedback is currently being collected in preparation for further evaluation and refinement of the VCAP model.

  3. Daily Rhythms in Mosquitoes and Their Consequences for Malaria Transmission

    PubMed Central

    Rund, Samuel S. C.; O’Donnell, Aidan J.; Gentile, James E.; Reece, Sarah E.

    2016-01-01

    The 24-h day involves cycles in environmental factors that impact organismal fitness. This is thought to select for organisms to regulate their temporal biology accordingly, through circadian and diel rhythms. In addition to rhythms in abiotic factors (such as light and temperature), biotic factors, including ecological interactions, also follow daily cycles. How daily rhythms shape, and are shaped by, interactions between organisms is poorly understood. Here, we review an emerging area, namely the causes and consequences of daily rhythms in the interactions between vectors, their hosts and the parasites they transmit. We focus on mosquitoes, malaria parasites and vertebrate hosts, because this system offers the opportunity to integrate from genetic and molecular mechanisms to population dynamics and because disrupting rhythms offers a novel avenue for disease control. PMID:27089370

  4. Genetic approaches to interfere with malaria transmission by vector mosquitoes

    PubMed Central

    Wang, Sibao; Jacobs-Lorena, Marcelo

    2013-01-01

    Malaria remains one of the world’s most devastating diseases, causing over one million deaths every year. The most vulnerable stages of Plasmodium development in the vector mosquito occur in the midgut lumen, making the midgut a prime target for intervention. Mosquito transgenesis and paratransgenesis are two novel strategies that aim at rendering the vector incapable of sustaining Plasmodium development. Mosquito transgenesis involves direct genetic engineering of the mosquito itself for delivery of anti-Plasmodium effector molecules. Conversely, paratransgenesis involves the genetic modification of mosquito symbionts for expression of anti-pathogen effector molecules. Here we consider both genetic manipulation strategies for rendering mosquitoes refractory to Plasmodium infection, and discuss challenges for the translation of laboratory findings to field applications. PMID:23395485

  5. Daily Rhythms in Mosquitoes and Their Consequences for Malaria Transmission.

    PubMed

    Rund, Samuel S C; O'Donnell, Aidan J; Gentile, James E; Reece, Sarah E

    2016-04-14

    The 24-h day involves cycles in environmental factors that impact organismal fitness. This is thought to select for organisms to regulate their temporal biology accordingly, through circadian and diel rhythms. In addition to rhythms in abiotic factors (such as light and temperature), biotic factors, including ecological interactions, also follow daily cycles. How daily rhythms shape, and are shaped by, interactions between organisms is poorly understood. Here, we review an emerging area, namely the causes and consequences of daily rhythms in the interactions between vectors, their hosts and the parasites they transmit. We focus on mosquitoes, malaria parasites and vertebrate hosts, because this system offers the opportunity to integrate from genetic and molecular mechanisms to population dynamics and because disrupting rhythms offers a novel avenue for disease control.

  6. Genetic approaches to interfere with malaria transmission by vector mosquitoes.

    PubMed

    Wang, Sibao; Jacobs-Lorena, Marcelo

    2013-03-01

    Malaria remains one of the most devastating diseases worldwide, causing over 1 million deaths every year. The most vulnerable stages of Plasmodium development in the vector mosquito occur in the midgut lumen, making the midgut a prime target for intervention. Mosquito transgenesis and paratransgenesis are two novel strategies that aim at rendering the vector incapable of sustaining Plasmodium development. Mosquito transgenesis involves direct genetic engineering of the mosquito itself for delivery of anti-Plasmodium effector molecules. Conversely, paratransgenesis involves the genetic modification of mosquito symbionts for expression of anti-pathogen effector molecules. Here we consider both genetic manipulation strategies for rendering mosquitoes refractory to Plasmodium infection, and discuss challenges for the translation of laboratory findings to field applications.

  7. Simulating the spread of malaria using a generic transmission model for mosquito-borne infectious diseases

    NASA Astrophysics Data System (ADS)

    Kon, Cynthia Mui Lian; Labadin, Jane

    2016-06-01

    Malaria is a critical infection caused by parasites which are spread to humans through mosquito bites. Approximately half of the world's population is in peril of getting infected by malaria. Mosquito-borne diseases have a standard behavior where they are transmitted in the same manner, only through vector mosquito. Taking this into account, a generic spatial-temporal model for transmission of multiple mosquito-borne diseases had been formulated. Our interest is to reproduce the actual cases of different mosquito-borne diseases using the generic model and then predict future cases so as to improve control and target measures competently. In this paper, we utilize notified weekly malaria cases in four districts in Sarawak, Malaysia, namely Kapit, Song, Belaga and Marudi. The actual cases for 36 weeks, which is from week 39 in 2012 to week 22 in 2013, are compared with simulations of the generic spatial-temporal transmission mosquito-borne diseases model. We observe that the simulation results display corresponding result to the actual malaria cases in the four districts.

  8. Malaria PCR detection in Cambodian low-transmission settings: dried blood spots versus venous blood samples.

    PubMed

    Canier, Lydie; Khim, Nimol; Kim, Saorin; Eam, Rotha; Khean, Chanra; Loch, Kaknika; Ken, Malen; Pannus, Pieter; Bosman, Philippe; Stassijns, Jorgen; Nackers, Fabienne; Alipon, SweetC; Char, Meng Chuor; Chea, Nguon; Etienne, William; De Smet, Martin; Kindermans, Jean-Marie; Ménard, Didier

    2015-03-01

    In the context of malaria elimination, novel strategies for detecting very low malaria parasite densities in asymptomatic individuals are needed. One of the major limitations of the malaria parasite detection methods is the volume of blood samples being analyzed. The objective of the study was to compare the diagnostic accuracy of a malaria polymerase chain reaction assay, from dried blood spots (DBS, 5 μL) and different volumes of venous blood (50 μL, 200 μL, and 1 mL). The limit of detection of the polymerase chain reaction assay, using calibrated Plasmodium falciparum blood dilutions, showed that venous blood samples (50 μL, 200 μL, 1 mL) combined with Qiagen extraction methods gave a similar threshold of 100 parasites/mL, ∼100-fold lower than 5 μL DBS/Instagene method. On a set of 521 field samples, collected in two different transmission areas in northern Cambodia, no significant difference in the proportion of parasite carriers, regardless of the methods used was found. The 5 μL DBS method missed 27% of the samples detected by the 1 mL venous blood method, but most of the missed parasites carriers were infected by Plasmodium vivax (84%). The remaining missed P. falciparum parasite carriers (N = 3) were only detected in high-transmission areas.

  9. Transmission and control of vivax malaria in Afghan refugee settlements in Pakistan.

    PubMed

    Rowland, M; Hewitt, S; Durrani, N; Bano, N; Wirtz, R

    1997-01-01

    Regular biting collections were conducted in 1993-1994 to investigate seasonal fluctuations in the abundance of anophelines in Afghan refugee villages in north-western Pakistan. Enzyme-linked immunosorbent assay were used to test heads-plus-thoraces for the presence of malaria sporozoites. Anophelines giving positive results for Plasmodium vivax were captured in every month except January. Nine species were positive. Biting rates showed a marked increase in May, after the spring rains, and thus spring transmission of vivax malaria seems certain. However, transmission of vivax malaria reached its peak only after the monsoon in July. To determine the optimal time to control vivax malaria by indoor spraying with residual insecticide, spray campaigns were conducted in either spring or summer in 14 refugee villages. Villages sprayed in July 1994 showed a mean reduction in annual incidence of 62% (95% confidence interval [CI] +/-6%) relative to the previous year, whereas villages sprayed in April 1994 showed only a 15% reduction (95% CI +/- 32%). Parasite prevalence surveys conducted in April and October 1994 confirmed the greater efficacy of spray campaigns waged in July. The insecticide malathion proved as effective as the pyrethroid lambdacyhalothrin, even though several species of anopheline were resistant to malathion.

  10. Modelling entomological-climatic interactions of Plasmodium falciparum malaria transmission in two Colombian endemic-regions: contributions to a National Malaria Early Warning System

    PubMed Central

    Ruiz, Daniel; Poveda, Germán; Vélez, Iván D; Quiñones, Martha L; Rúa, Guillermo L; Velásquez, Luz E; Zuluaga, Juan S

    2006-01-01

    Background Malaria has recently re-emerged as a public health burden in Colombia. Although the problem seems to be climate-driven, there remain significant gaps of knowledge in the understanding of the complexity of malaria transmission, which have motivated attempts to develop a comprehensive model. Methods The mathematical tool was applied to represent Plasmodium falciparum malaria transmission in two endemic-areas. Entomological exogenous variables were estimated through field campaigns and laboratory experiments. Availability of breeding places was included towards representing fluctuations in vector densities. Diverse scenarios, sensitivity analyses and instabilities cases were considered during experimentation-validation process. Results Correlation coefficients and mean square errors between observed and modelled incidences reached 0.897–0.668 (P > 0.95) and 0.0002–0.0005, respectively. Temperature became the most relevant climatic parameter driving the final incidence. Accordingly, malaria outbreaks are possible during the favourable epochs following the onset of El Niño warm events. Sporogonic and gonotrophic cycles showed to be the entomological key-variables controlling the transmission potential of mosquitoes' population. Simulation results also showed that seasonality of vector density becomes an important factor towards understanding disease transmission. Conclusion The model constitutes a promising tool to deepen the understanding of the multiple interactions related to malaria transmission conducive to outbreaks. In the foreseeable future it could be implemented as a tool to diagnose possible dynamical patterns of malaria incidence under several scenarios, as well as a decision-making tool for the early detection and control of outbreaks. The model will be also able to be merged with forecasts of El Niño events to provide a National Malaria Early Warning System. PMID:16882349

  11. School-based surveys of malaria in Oromia Regional State, Ethiopia: a rapid survey method for malaria in low transmission settings

    PubMed Central

    2011-01-01

    Background In Ethiopia, malaria transmission is seasonal and unstable, with both Plasmodium falciparum and Plasmodium vivax endemic. Such spatial and temporal clustering of malaria only serves to underscore the importance of regularly collecting up-to-date malaria surveillance data to inform decision-making in malaria control. Cross-sectional school-based malaria surveys were conducted across Oromia Regional State to generate up-to-date data for planning malaria control interventions, as well as monitoring and evaluation of operational programme implementation. Methods Two hundred primary schools were randomly selected using a stratified and weighted sampling frame; 100 children aged five to 18 years were then randomly chosen within each school. Surveys were carried out in May 2009 and from October to December 2009, to coincide with the peak of malaria transmission in different parts of Oromia. Each child was tested for malaria by expert microscopy, their haemoglobin measured and a simple questionnaire completed. Satellite-derived environmental data were used to assess ecological correlates of Plasmodium infection; Bayesian geostatistical methods and Kulldorff's spatial scan statistic were employed to investigate spatial heterogeneity. Results A total 20,899 children from 197 schools provided blood samples, two selected schools were inaccessible and one school refused to participate. The overall prevalence of Plasmodium infection was found to be 0.56% (95% CI: 0.46-0.67%), with 53% of infections due to P. falciparum and 47% due to P. vivax. Of children surveyed, 17.6% (95% CI: 17.0-18.1%) were anaemic, while 46% reported sleeping under a mosquito net the previous night. Malaria was found at 30 (15%) schools to a maximum elevation of 2,187 metres, with school-level Plasmodium prevalence ranging between 0% and 14.5%. Although environmental variables were only weakly associated with P. falciparum and P. vivax infection, clusters of infection were identified within

  12. Efficient block error concealment code for image and video transmission

    NASA Astrophysics Data System (ADS)

    Min, Jungki; Chan, Andrew K.

    1999-05-01

    Image and video compression standards such as JPEG, MPEG, H.263 are highly sensitive to error during transmission. Among typical error propagation mechanisms in video compression schemes, loss of block synchronization produces the worst image degradation. Even an error of a single bit in block synchronization may result in data to be placed in wrong positions that is caused by spatial shifts. Our proposed efficient block error concealment code (EBECC) virtually guarantees block synchronization and it improves coding efficiency by several hundred folds over the error resilient entropy code (EREC), proposed by N. G. Kingsbury and D. W. Redmill, depending on the image format and size. In addition, the EBECC produces slightly better resolution on the reconstructed images or video frames than those from the EREC. Another important advantage of the EBECC is that it does not require redundancy contrasting to the EREC that requires 2-3 percent of redundancy. Our preliminary results show the EBECC is 240 times faster than EREC for encoding and 330 times for decoding based on the CIF format of H.263 video coding standard. The EBECC can be used on most of the popular image and video compression schemes such as JPEG, MPEG, and H.263. Additionally, it is especially useful to wireless networks in which the percentage of image and video data is high.

  13. Probable autochthonous Plasmodium vivax malaria transmission in Michigan: case report and epidemiological investigation.

    PubMed

    Sunstrum, J; Elliott, L J; Barat, L M; Walker, E D; Zucker, J R

    2001-12-01

    In September 1995, a Michigan resident with no history of international travel was diagnosed with Plasmodium vivax infection, and local mosquito-borne transmission was suspected. An epidemiological investigation did not identify additional cases of local transmission, and there was no apparent link to the 12 imported malaria cases detected in the region. Potential sites of nighttime outdoor exposure included a campground in a swampy area, close to a racetrack frequented by international travelers, some of whom were known to come from countries with malaria transmission. Entomological investigation identified Anopheles spp. larvae and adults near the campsite. Summer temperatures 4.2 degrees C above average would have contributed to shortened maturation time of P. vivax within the insect vector, increasing the likelihood of infectivity. These investigations indicated that this patient probably acquired P. vivax infection through the bite of a locally infected Anopheles spp. mosquito. Physicians need to consider malaria as a possible cause of unexplained febrile illness, even in the absence of international travel, particularly during the summer months.

  14. Attributing Climate Conditions for Stable Malaria Transmission to Human Activity in sub-Saharan Africa

    NASA Astrophysics Data System (ADS)

    Sheldrake, L.; Mitchell, D.; Allen, M. R.

    2015-12-01

    Temperature and precipitation limit areas of stable malaria transmission, but the effects of climate change on the disease remain controversial. Previously, studies have not separated the influence of anthropogenic climate change and natural variability, despite being an essential step in the attribution of climate change impacts. Ensembles of 2900 simulations of regional climate in sub-Saharan Africa for the year 2013, one representing realistic conditions and the other how climate might have been in the absence of human influence, were used to force a P.falciparium climate suitability model developed by the Mapping Malaria Risk in Africa project. Strongest signals were detected in areas of unstable transmission, indicating their heightened sensitivity to climatic factors. Evidently, impacts of human-induced climate change were unevenly distributed: the probability of conditions being suitable for stable malaria transmission were substantially reduced (increased) in the Sahel (Greater Horn of Africa (GHOA), particularly in the Ethiopian and Kenyan highlands). The length of the transmission season was correspondingly shortened in the Sahel and extended in the GHOA, by 1 to 2 months, including in Kericho (Kenya), where the role of climate change in driving recent malaria occurrence is hotly contested. Human-induced warming was primarily responsible for positive anomalies in the GHOA, while reduced rainfall caused negative anomalies in the Sahel. The latter was associated with anthropogenic impacts on the West African Monsoon, but uncertainty in the RCM's ability to reproduce precipitation trends in the region weakens confidence in the result. That said, outputs correspond well with broad-scale changes in observed endemicity, implying a potentially important contribution of anthropogenic climate change to the malaria burden during the past century. Results support the health-framing of climate risk and help indicate hotspots of climate vulnerability, providing

  15. Malaria

    MedlinePlus

    ... a parasite. You get it when an infected mosquito bites you. Malaria is a major cause of ... insect repellent with DEET Cover up Sleep under mosquito netting Centers for Disease Control and Prevention

  16. Malaria

    MedlinePlus

    ... Malaria can be carried by mosquitoes in temperate climates, but the parasite disappears over the winter. The ... a major disease hazard for travelers to warm climates. In some areas of the world, mosquitoes that ...

  17. Malaria

    DTIC Science & Technology

    2011-06-01

    established, the infection is classi- fied as cryptic malaria. A large majority of infections are transmitted by the bite of an infected female ... female anopheline mosquitoes. Plasmodium sp infecting humans include Plasmodium vivax, Plasmodium falci- parum, Plasmodium malariae, and Plasmodium ovale...paled and pigment formed within them. Later he observed male gametes form by exflagellation and described the male and female gam- etes, the

  18. A mechanistic approach for accurate simulation of village scale malaria transmission

    PubMed Central

    Bomblies, Arne; Duchemin, Jean-Bernard; Eltahir, Elfatih AB

    2009-01-01

    Background Malaria transmission models commonly incorporate spatial environmental and climate variability for making regional predictions of disease risk. However, a mismatch of these models' typical spatial resolutions and the characteristic scale of malaria vector population dynamics may confound disease risk predictions in areas of high spatial hydrological variability such as the Sahel region of Africa. Methods Field observations spanning two years from two Niger villages are compared. The two villages are separated by only 30 km but exhibit a ten-fold difference in anopheles mosquito density. These two villages would be covered by a single grid cell in many malaria models, yet their entomological activity differs greatly. Environmental conditions and associated entomological activity are simulated at high spatial- and temporal resolution using a mechanistic approach that couples a distributed hydrology scheme and an entomological model. Model results are compared to regular field observations of Anopheles gambiae sensu lato mosquito populations and local hydrology. The model resolves the formation and persistence of individual pools that facilitate mosquito breeding and predicts spatio-temporal mosquito population variability at high resolution using an agent-based modeling approach. Results Observations of soil moisture, pool size, and pool persistence are reproduced by the model. The resulting breeding of mosquitoes in the simulated pools yields time-integrated seasonal mosquito population dynamics that closely follow observations from captured mosquito abundance. Interannual difference in mosquito abundance is simulated, and the inter-village difference in mosquito population is reproduced for two years of observations. These modeling results emulate the known focal nature of malaria in Niger Sahel villages. Conclusion Hydrological variability must be represented at high spatial and temporal resolution to achieve accurate predictive ability of malaria risk

  19. Referral Patterns of Community Health Workers Diagnosing and Treating Malaria: Cluster-Randomized Trials in Two Areas of High- and Low-Malaria Transmission in Southwestern Uganda

    PubMed Central

    Lal, Sham; Ndyomugenyi, Richard; Magnussen, Pascal; Hansen, Kristian S.; Alexander, Neal D.; Paintain, Lucy; Chandramohan, Daniel; Clarke, Siân E.

    2016-01-01

    Malaria-endemic countries have implemented community health worker (CHW) programs to provide malaria diagnosis and treatment to populations living beyond the reach of health systems. However, there is limited evidence describing the referral practices of CHWs. We examined the impact of malaria rapid diagnostic tests (mRDTs) on CHW referral in two cluster-randomized trials, one conducted in a moderate-to-high malaria transmission setting and one in a low-transmission setting in Uganda, between January 2010 and July 2012. All CHWs were trained to prescribe artemisinin-based combination therapy (ACT) for malaria and recognize signs and symptoms for referral to health centers. CHWs in the control arm used a presumptive diagnosis for malaria based on clinical symptoms, whereas intervention arm CHWs used mRDTs. CHWs recorded ACT prescriptions, mRDT results, and referral in patient registers. An intention-to-treat analysis was undertaken using multivariable logistic regression. Referral was more frequent in the intervention arm versus the control arm (moderate-to-high transmission, P < 0.001; low transmission, P < 0.001). Despite this increase, referral advice was not always given when ACTs or prereferral rectal artesunate were prescribed: 14% prescribed rectal artesunate in the moderate-to-high setting were not referred. In addition, CHWs considered factors alongside mRDTs when referring. Child visits during the weekends or the rainy season were less likely to be referred, whereas visits to CHWs more distant from health centers were more likely to be referred (low transmission only). CHWs using mRDTs and ACTs increased referral compared with CHWs using a presumptive diagnosis. To address these concerns, referral training should be emphasized in CHW programs as they are scaled-up. PMID:27799650

  20. Impact of Irrigation Extension on Malaria Transmission in Simret, Tigray, Ethiopia

    PubMed Central

    Chung, Bonhee

    2016-01-01

    Poor subsistence farmers who live in a semi-arid area of northern Ethiopia build irrigation systems to overcome water shortages. However, there is a high risk of malaria transmission when increased standing water provides more favorable habitats for mosquito breeding. This is a serious problem because there are many barriers to malaria control measures and health care systems in the area. Using a causal loop diagram and computer simulations, the author attempted to visually illustrate positive and negative feedbacks between mosquito and human populations in the context of Simret, which is a small village located in northern Ethiopia and is generally considered a malaria-free area. The simulation results show that the number of infectious mosquitos increases to 17,215 at its peak, accounting for 3.5% of potentially dangerous mosquitos. At the same time, the number of sick people increases to 574 at its peak, accounting for 15% of local population. The malaria outbreak is controlled largely because of a fixed number of vulnerable people or local population that acts as an intermediate host. PMID:27658590

  1. Mapping malaria transmission risk in northern morocco using entomological and environmental data.

    PubMed

    Adlaoui, E; Faraj, C; El Bouhmi, M; El Aboudi, A; Ouahabi, S; Tran, A; Fontenille, D; El Aouad, R

    2011-01-01

    Malaria resurgence risk in Morocco depends, among other factors, on environmental changes as well as the introduction of parasite carriers. The aim of this paper is to analyze the receptivity of the Loukkos area, large wetlands in Northern Morocco, to quantify and to map malaria transmission risk in this region using biological and environmental data. This risk was assessed on entomological risk basis and was mapped using environmental markers derived from satellite imagery. Maps showing spatial and temporal variations of entomological risk for Plasmodium vivax and P. falciparum were produced. Results showed this risk to be highly seasonal and much higher in rice fields than in swamps. This risk is lower for Afrotropical P. falciparum strains because of the low infectivity of Anopheles labranchiae, principal malaria vector in Morocco. However, it is very high for P. vivax mainly during summer corresponding to the rice cultivation period. Although the entomological risk is high in Loukkos region, malaria resurgence risk remains very low, because of the low vulnerability of the area.

  2. Apparent vector-mediated parent-to-offspring transmission in an avian malaria-like parasite.

    PubMed

    Chakarov, Nayden; Linke, Burkhard; Boerner, Martina; Goesmann, Alexander; Krüger, Oliver; Hoffman, Joseph I

    2015-03-01

    Parasite transmission strategies strongly impact host-parasite co-evolution and virulence. However, studies of vector-borne parasites such as avian malaria have neglected the potential effects of host relatedness on the exchange of parasites. To test whether extended parental care in the presence of vectors increases the probability of transmission from parents to offspring, we used high-throughput sequencing to develop microsatellites for malaria-like Leucocytozoon parasites of a wild raptor population. We show that host siblings carry genetically more similar parasites than unrelated chicks both within and across years. Moreover, chicks of mothers of the same plumage morph carried more similar parasites than nestlings whose mothers were of different morphs, consistent with matrilineal transmission of morph-specific parasite strains. Ours is the first evidence of an association between host relatedness and parasite genetic similarity, consistent with vector-mediated parent-to-offspring transmission. The conditions for such 'quasi-vertical' transmission may be common and could suppress the evolution of pathogen virulence.

  3. Vaccines Against Malaria

    PubMed Central

    Ouattara, Amed; Laurens, Matthew B.

    2015-01-01

    Despite global efforts to control malaria, the illness remains a significant public health threat. Currently, there is no licensed vaccine against malaria, but an efficacious vaccine would represent an important public health tool for successful malaria elimination. Malaria vaccine development continues to be hindered by a poor understanding of antimalarial immunity, a lack of an immune correlate of protection, and the genetic diversity of malaria parasites. Current vaccine development efforts largely target Plasmodium falciparum parasites in the pre-erythrocytic and erythrocytic stages, with some research on transmission-blocking vaccines against asexual stages and vaccines against pregnancy-associated malaria. The leading pre-erythrocytic vaccine candidate is RTS,S, and early results of ongoing Phase 3 testing show overall efficacy of 46% against clinical malaria. The next steps for malaria vaccine development will focus on the design of a product that is efficacious against the highly diverse strains of malaria and the identification of a correlate of protection against disease. PMID:25452593

  4. Clinical Malaria Transmission Trends and Its Association with Climatic Variables in Tubu Village, Botswana: A Retrospective Analysis

    PubMed Central

    Chimbari, Moses John; Ngwenya, Barbara Ntombi; Sartorius, Benn

    2016-01-01

    Good knowledge on the interactions between climatic variables and malaria can be very useful for predicting outbreaks and preparedness interventions. We investigated clinical malaria transmission patterns and its temporal relationship with climatic variables in Tubu village, Botswana. A 5-year retrospective time series data analysis was conducted to determine the transmission patterns of clinical malaria cases at Tubu Health Post and its relationship with rainfall, flood discharge, flood extent, mean minimum, maximum and average temperatures. Data was obtained from clinical records and respective institutions for the period July 2005 to June 2010, presented graphically and analysed using the Univariate ANOVA and Pearson cross-correlation coefficient tests. Peak malaria season occurred between October and May with the highest cumulative incidence of clinical malaria cases being recorded in February. Most of the cases were individuals aged >5 years. Associations between the incidence of clinical malaria cases and several factors were strong at lag periods of 1 month; rainfall (r = 0.417), mean minimum temperature (r = 0.537), mean average temperature (r = 0.493); and at lag period of 6 months for flood extent (r = 0.467) and zero month for flood discharge (r = 0.497). The effect of mean maximum temperature was strongest at 2-month lag period (r = 0.328). Although malaria transmission patterns varied from year to year the trends were similar to those observed in sub-Saharan Africa. Age group >5 years experienced the greatest burden of clinical malaria probably due to the effects of the national malaria elimination programme. Rainfall, flood discharge and extent, mean minimum and mean average temperatures showed some correlation with the incidence of clinical malaria cases. PMID:26983035

  5. Partnering for impact: Integrated transmission assessment surveys for lymphatic filariasis, soil transmitted helminths and malaria in Haiti

    PubMed Central

    Lemoine, Jean Frantz; Monestime, Franck; Fayette, Carl R.; Direny, Abdel N.; Desir, Luccene; Beau de Rochars, Valery E.; Streit, Thomas G.; Renneker, Kristen; Chu, Brian K.; Chang, Michelle A.; Mace, Kimberly E.; Won, Kimberly Y.; Lammie, Patrick J.

    2017-01-01

    Background Since 2001, Haiti’s National Program for the Elimination of Lymphatic Filariasis (NPELF) has worked to reduce the transmission of lymphatic filariasis (LF) through annual mass drug administration (MDA) with diethylcarbamazine and albendazole. The NPELF reached full national coverage with MDA for LF in 2012, and by 2014, a total of 14 evaluation units (48 communes) had met WHO eligibility criteria to conduct LF transmission assessment surveys (TAS) to determine whether prevalence had been reduced to below a threshold, such that transmission is assumed to be no longer sustainable. Haiti is also endemic for malaria and many communities suffer a high burden of soil transmitted helminths (STH). Heeding the call from WHO for integration of neglected tropical diseases (NTD) activities, Haiti’s NPELF worked with the national malaria control program (NMCP) and with partners to develop an integrated TAS (LF-STH-malaria) to include assessments for malaria and STH. Methodology/Principle findings The aim of this study was to evaluate the feasibility of using TAS surveys for LF as a platform to collect information about STH and malaria. Between November 2014 and June 2015, TAS were conducted in 14 evaluation units (EUs) including 1 TAS (LF-only), 1 TAS-STH-malaria, and 12 TAS-malaria, with a total of 16,655 children tested for LF, 14,795 tested for malaria, and 298 tested for STH. In all, 12 of the 14 EUs passed the LF TAS, allowing the program to stop MDA for LF in 44 communes. The EU where children were also tested for STH will require annual school-based treatment with albendazole to maintain reduced STH levels. Finally, only 12 of 14,795 children tested positive for malaria by RDT in 38 communes. Conclusions/Significance Haiti’s 2014–2015 Integrated TAS surveys provide evidence of the feasibility of using the LF TAS as a platform for integration of assessments for STH and or malaria. PMID:28207792

  6. Application of Serological Tools and Spatial Analysis to Investigate Malaria Transmission Dynamics in Highland Areas of Southwest Uganda

    PubMed Central

    Lynch, Caroline A.; Cook, Jackie; Nanyunja, Sarah; Bruce, Jane; Bhasin, Amit; Drakeley, Chris; Roper, Cally; Pearce, Richard; Rwakimari, John B.; Abeku, Tarekegn A.; Corran, Patrick; Cox, Jonathan

    2016-01-01

    Serological markers, combined with spatial analysis, offer a comparatively more sensitive means by which to measure and detect foci of malaria transmission in highland areas than traditional malariometric indicators. Plasmodium falciparum parasite prevalence, seroprevalence, and seroconversion rate to P. falciparum merozoite surface protein-119 (MSP-119) were measured in a cross-sectional survey to determine differences in transmission between altitudinal strata. Clusters of P. falciparum parasite prevalence and high antibody responses to MSP-119 were detected and compared. Results show that P. falciparum prevalence and seroprevalence generally decreased with increasing altitude. However, transmission was heterogeneous with hotspots of prevalence and/or seroprevalence detected in both highland and highland fringe altitudes, including a serological hotspot at 2,200 m. Results demonstrate that seroprevalence can be used as an additional tool to identify hotspots of malaria transmission that might be difficult to detect using traditional cross-sectional parasite surveys or through vector studies. Our study findings identify ways in which malaria prevention and control can be more effectively targeted in highland or low transmission areas via serological measures. These tools will become increasingly important for countries with an elimination agenda and/or where malaria transmission is becoming patchy and focal, but receptivity to malaria transmission remains high. PMID:27022156

  7. Parasitological Indices of Malaria Transmission in Children under Fifteen Years in Two Ecoepidemiological Zones in Southwestern Burkina Faso

    PubMed Central

    Sangaré, Ibrahim; Coulibaly, Sanata; Namountougou, Moussa; Paré-Toé, Léa; Ouédraogo, Anicet Georges; Diabaté, Abdoulaye; Foy, Brian D.

    2017-01-01

    Twenty years after the latest publications performed on the parasitological indices of malaria transmission in northwest of the second city of Burkina Faso, it was important to update the epidemiological profile of malaria in children under the age of 15 years. The objective of this study was to determine and compare the parasitological parameters of malaria transmission by season, area, and age in the two zones (rice and savanna) in the northwest of Bobo-Dioulasso, Burkina Faso. Overall, the results showed that there was no significant difference in the parasitological indices of malaria transmission within children under fifteen years between the rice site and the savannah site and whatever the season (P > 0.05). The profound environmental modifications that occurred in the rice zone would have led to changes in vector behavior and consequently to changes in the epidemiological profile of malaria, contrary to the results obtained since the last publications. An entomological study correlated with this study is therefore necessary for effective decision-making for the malaria control in both areas. Future research must now focus on the impact that these profound environmental modifications of rice area are having on malaria control in Burkina Faso. PMID:28286526

  8. An overview of malaria transmission from the perspective of Amazon Anopheles vectors

    PubMed Central

    Pimenta, Paulo FP; Orfano, Alessandra S; Bahia, Ana C; Duarte, Ana PM; Ríos-Velásquez, Claudia M; Melo, Fabrício F; Pessoa, Felipe AC; Oliveira, Giselle A; Campos, Keillen MM; Villegas, Luis Martínez; Rodrigues, Nilton Barnabé; Nacif-Pimenta, Rafael; Simões, Rejane C; Monteiro, Wuelton M; Amino, Rogerio; Traub-Cseko, Yara M; Lima, José BP; Barbosa, Maria GV; Lacerda, Marcus VG; Tadei, Wanderli P; Secundino, Nágila FC

    2015-01-01

    In the Americas, areas with a high risk of malaria transmission are mainly located in the Amazon Forest, which extends across nine countries. One keystone step to understanding the Plasmodium life cycle in Anopheles species from the Amazon Region is to obtain experimentally infected mosquito vectors. Several attempts to colonise Ano- pheles species have been conducted, but with only short-lived success or no success at all. In this review, we review the literature on malaria transmission from the perspective of its Amazon vectors. Currently, it is possible to develop experimental Plasmodium vivax infection of the colonised and field-captured vectors in laboratories located close to Amazonian endemic areas. We are also reviewing studies related to the immune response to P. vivax infection of Anopheles aquasalis, a coastal mosquito species. Finally, we discuss the importance of the modulation of Plasmodium infection by the vector microbiota and also consider the anopheline genomes. The establishment of experimental mosquito infections with Plasmodium falciparum, Plasmodium yoelii and Plasmodium berghei parasites that could provide interesting models for studying malaria in the Amazonian scenario is important. Understanding the molecular mechanisms involved in the development of the parasites in New World vectors is crucial in order to better determine the interaction process and vectorial competence. PMID:25742262

  9. Combination therapy counteracts the enhanced transmission of drug-resistant malaria parasites to mosquitoes.

    PubMed

    Hallett, Rachel L; Sutherland, Colin J; Alexander, Neal; Ord, Rosalynn; Jawara, Musa; Drakeley, Chris J; Pinder, Margaret; Walraven, Gijs; Targett, Geoffrey A T; Alloueche, Ali

    2004-10-01

    Malaria parasites carrying genes conferring resistance to antimalarials are thought to have a selective advantage which leads to higher rates of transmissibility from the drug-treated host. This is a likely mechanism for the increasing prevalence of parasites with resistance to chloroquine (CQ) and sulfadoxine-pyrimethamine in sub-Saharan Africa. Combination therapy is the key strategy being implemented to reduce the impact of resistance, but its effect on the transmission of genetically resistant parasites from treated patients to mosquito vectors has not been measured directly. In a trial comparing CQ monotherapy to the combination CQ plus artesunate (AS) in Gambian children with uncomplicated falciparum malaria, we measured transmissibility by feeding Anopheles gambiae mosquitoes with blood from 43 gametocyte-positive patients through a membrane. In the CQ-treated group, gametocytes from patients carrying parasites with the CQ resistance-associated allele pfcrt-76T prior to treatment produced infected mosquitoes with 38 times higher Plasmodium falciparum oocyst burdens than mosquitoes fed on gametocytes from patients infected with sensitive parasites (P < 0.001). Gametocytes from parasites carrying the resistance-associated allele pfmdr1-86Y produced 14-fold higher oocyst burdens than gametocytes from patients infected with sensitive parasites (P = 0.011). However, parasites carrying either of these resistance-associated alleles pretreatment were not associated with higher mosquito oocyst burdens in the CQ-AS-treated group. Thus, combination therapy overcomes the transmission advantage enjoyed by drug-resistant parasites.

  10. Rapid onset of transmission-reducing antibodies in javanese migrants exposed to malaria in papua, indonesia.

    PubMed

    Bousema, J Teun; Roeffen, Will; van der Kolk, Mike; de Vlas, Sake J; van de Vegte-Bolmer, Marga; Bangs, Michael J; Teelen, Karina; Kurniawan, Liliana; Maguire, Jason D; Baird, J Kevin; Sauerwein, Robert W

    2006-03-01

    Transmission of Plasmodium falciparum malaria is initiated by sexual stages in the mosquito. Anti-Pfs48/45 and anti-Pfs230 sexual stage antibodies that are ingested together with parasites can reduce parasite development and subsequently malaria transmission. Acquisition of sexual stage immunity was studied in a cohort of 102 non-immune Javanese individuals migrating to hyperendemic Papua Indonesia. Seroprevalence of antibodies against Pfs48/45 and Pfs230 and functional transmission-reducing activity (TRA) were measured upon arrival and at 6, 12, and 24 months. Asexual parasitemia and gametocytemia were assessed every two weeks. The TRA and seroreactivity increased with the number of P. falciparum infections. The longitudinally sustained association between TRA and antibodies against Pfs48/45 (odds ratio [OR] = 3.74, 95% confidence interval [CI] = 1.51-9.29) and Pfs230 (OR = 3.72, 95% CI = 1.36-10.17) suggests that functional transmission reducing immunity is acquired after limited exposure to infection.

  11. Entomological Monitoring and Evaluation: Diverse Transmission Settings of ICEMR Projects Will Require Local and Regional Malaria Elimination Strategies.

    PubMed

    Conn, Jan E; Norris, Douglas E; Donnelly, Martin J; Beebe, Nigel W; Burkot, Thomas R; Coulibaly, Mamadou B; Chery, Laura; Eapen, Alex; Keven, John B; Kilama, Maxwell; Kumar, Ashwani; Lindsay, Steve W; Moreno, Marta; Quinones, Martha; Reimer, Lisa J; Russell, Tanya L; Smith, David L; Thomas, Matthew B; Walker, Edward D; Wilson, Mark L; Yan, Guiyun

    2015-09-01

    The unprecedented global efforts for malaria elimination in the past decade have resulted in altered vectorial systems, vector behaviors, and bionomics. These changes combined with increasingly evident heterogeneities in malaria transmission require innovative vector control strategies in addition to the established practices of long-lasting insecticidal nets and indoor residual spraying. Integrated vector management will require focal and tailored vector control to achieve malaria elimination. This switch of emphasis from universal coverage to universal coverage plus additional interventions will be reliant on improved entomological monitoring and evaluation. In 2010, the National Institutes for Allergies and Infectious Diseases (NIAID) established a network of malaria research centers termed ICEMRs (International Centers for Excellence in Malaria Research) expressly to develop this evidence base in diverse malaria endemic settings. In this article, we contrast the differing ecology and transmission settings across the ICEMR study locations. In South America, Africa, and Asia, vector biologists are already dealing with many of the issues of pushing to elimination such as highly focal transmission, proportionate increase in the importance of outdoor and crepuscular biting, vector species complexity, and "sub patent" vector transmission.

  12. Entomological Monitoring and Evaluation: Diverse Transmission Settings of ICEMR Projects Will Require Local and Regional Malaria Elimination Strategies

    PubMed Central

    Conn, Jan E.; Norris, Douglas E.; Donnelly, Martin J.; Beebe, Nigel W.; Burkot, Thomas R.; Coulibaly, Mamadou B.; Chery, Laura; Eapen, Alex; Keven, John B.; Kilama, Maxwell; Kumar, Ashwani; Lindsay, Steve W.; Moreno, Marta; Quinones, Martha; Reimer, Lisa J.; Russell, Tanya L.; Smith, David L.; Thomas, Matthew B.; Walker, Edward D.; Wilson, Mark L.; Yan, Guiyun

    2015-01-01

    The unprecedented global efforts for malaria elimination in the past decade have resulted in altered vectorial systems, vector behaviors, and bionomics. These changes combined with increasingly evident heterogeneities in malaria transmission require innovative vector control strategies in addition to the established practices of long-lasting insecticidal nets and indoor residual spraying. Integrated vector management will require focal and tailored vector control to achieve malaria elimination. This switch of emphasis from universal coverage to universal coverage plus additional interventions will be reliant on improved entomological monitoring and evaluation. In 2010, the National Institutes for Allergies and Infectious Diseases (NIAID) established a network of malaria research centers termed ICEMRs (International Centers for Excellence in Malaria Research) expressly to develop this evidence base in diverse malaria endemic settings. In this article, we contrast the differing ecology and transmission settings across the ICEMR study locations. In South America, Africa, and Asia, vector biologists are already dealing with many of the issues of pushing to elimination such as highly focal transmission, proportionate increase in the importance of outdoor and crepuscular biting, vector species complexity, and “sub patent” vector transmission. PMID:26259942

  13. Fever treatment in the absence of malaria transmission in an urban informal settlement in Nairobi, Kenya

    PubMed Central

    Ye, Yazoume; Madise, Nyovani; Ndugwa, Robert; Ochola, Sam; Snow, Robert W

    2009-01-01

    Background In sub-Saharan Africa, knowledge of malaria transmission across rapidly proliferating urban centres and recommendations for its prevention or management remain poorly defined. This paper presents the results of an investigation into infection prevalence and treatment of recent febrile events among a slum population in Nairobi, Kenya. Methods In July 2008, a community-based malaria parasite prevalence survey was conducted in Korogocho slum, which forms part of the Nairobi Urban Health and Demographic Surveillance system. Interviewers visited 1,069 participants at home and collected data on reported fevers experienced over the preceding 14 days and details on the treatment of these episodes. Each participant was tested for malaria parasite presence with Rapid Diagnostic Test (RDT) and microscopy. Descriptive analyses were performed to assess the period prevalence of reported fever episodes and treatment behaviour. Results Of the 1,069 participants visited, 983 (92%) consented to be tested. Three were positive for Plasmodium falciparum using RDT; however, all were confirmed negative on microscopy. Microscopic examination of all 953 readable slides showed zero prevalence. Overall, from the 1,004 participants who have data on fever, 170 fever episodes were reported giving a relatively high period prevalence (16.9%, 95% CI:13.9%–20.5%) and higher among children below five years (20.1%, 95%CI:13.8%–27.8%). Of the fever episodes with treatment information 54.3% (95%CI:46.3%–62.2%) were treated as malaria using mainly sulphadoxine-pyrimethamine or amodiaquine, including those managed at a formal health facility. Only four episodes were managed using the nationally recommended first-line treatment, artemether-lumefantrine. Conclusion The study could not demonstrate any evidence of malaria in Korogocho, a slum in the centre of Nairobi. Fever was a common complaint and often treated as malaria with anti-malarial drugs. Strategies, including testing for malaria

  14. Prospects of intermittent preventive treatment of adults against malaria in areas of seasonal and unstable malaria transmission, and a possible role for chloroquine.

    PubMed

    Giha, Hayder A

    2010-04-01

    Chloroquine (CQ) is outmoded as an antimalarial drug in most of the malarial world because of the high resistance rate of parasites. The parasite resistance to CQ is attributed to pfcrt/pfmdr1 gene mutations. Recent studies showed that parasites with mutations of pfcrt/pfmdr1 genes are less virulent, and that those with dhfr/dhps mutations are more susceptible to host immune clearance; the former and latter mutations are linked. In the era of artemisinin-based combination therapy, the frequency of pfcrt/pfmdr1 wild variants is expected to rise. In areas of unstable malaria transmission, the unpredictable severe epidemics of malaria and epidemics of severe malaria could result in high mortality rate among the semi-immune population. With this in mind, the use of CQ for intermittent preventive treatment of adults (IPTa) is suggested as a feasible control measure to reduce malaria mortality in adults and older children without reducing uncomplicated malaria morbidity. The above is discussed in a multidisciplinary approach validating the deployment of molecular techniques in malaria control and showing a possible role for CQ as a rescue drug after being abandoned.

  15. Variation in relapse frequency and the transmission potential of Plasmodium vivax malaria

    PubMed Central

    White, Michael T.; Shirreff, George; Karl, Stephan; Ghani, Azra C.; Mueller, Ivo

    2016-01-01

    There is substantial variation in the relapse frequency of Plasmodium vivax malaria, with fast-relapsing strains in tropical areas, and slow-relapsing strains in temperate areas with seasonal transmission. We hypothesize that much of the phenotypic diversity in P. vivax relapses arises from selection of relapse frequency to optimize transmission potential in a given environment, in a process similar to the virulence trade-off hypothesis. We develop mathematical models of P. vivax transmission and calculate the basic reproduction number R0 to investigate how transmission potential varies with relapse frequency and seasonality. In tropical zones with year-round transmission, transmission potential is optimized at intermediate relapse frequencies of two to three months: slower-relapsing strains increase the opportunity for onward transmission to mosquitoes, but also increase the risk of being outcompeted by faster-relapsing strains. Seasonality is an important driver of relapse frequency for temperate strains, with the time to first relapse predicted to be six to nine months, coinciding with the duration between seasonal transmission peaks. We predict that there is a threshold degree of seasonality, below which fast-relapsing tropical strains are selected for, and above which slow-relapsing temperate strains dominate, providing an explanation for the observed global distribution of relapse phenotypes. PMID:27030414

  16. Variation in relapse frequency and the transmission potential of Plasmodium vivax malaria.

    PubMed

    White, Michael T; Shirreff, George; Karl, Stephan; Ghani, Azra C; Mueller, Ivo

    2016-03-30

    There is substantial variation in the relapse frequency of Plasmodium vivax malaria, with fast-relapsing strains in tropical areas, and slow-relapsing strains in temperate areas with seasonal transmission. We hypothesize that much of the phenotypic diversity in P. vivax relapses arises from selection of relapse frequency to optimize transmission potential in a given environment, in a process similar to the virulence trade-off hypothesis. We develop mathematical models of P. vivax transmission and calculate the basic reproduction number R0 to investigate how transmission potential varies with relapse frequency and seasonality. In tropical zones with year-round transmission, transmission potential is optimized at intermediate relapse frequencies of two to three months: slower-relapsing strains increase the opportunity for onward transmission to mosquitoes, but also increase the risk of being outcompeted by faster-relapsing strains. Seasonality is an important driver of relapse frequency for temperate strains, with the time to first relapse predicted to be six to nine months, coinciding with the duration between seasonal transmission peaks. We predict that there is a threshold degree of seasonality, below which fast-relapsing tropical strains are selected for, and above which slow-relapsing temperate strains dominate, providing an explanation for the observed global distribution of relapse phenotypes.

  17. Potent functional immunogenicity of Plasmodium falciparum transmission-blocking antigen (Pfs25) delivered with nanoemulsion and porous polymeric nanoparticles

    PubMed Central

    Kumar, Rajesh; Ledet, Grace; Graves, Richard; Datta, Dibyadyuti; Robinson, Shana; Bansal, Geetha P.; Mandal, Tarun; Kumar, Nirbhay

    2015-01-01

    Purpose To evaluate functional immunogenicity of CHrPfs25. a malaria transmission blocking vaccine antigen, using nanoemulsion and porous polymeric PLGA nanoparticles. Methods CHrPfs25 was formulated with nanoemulsions (NE) and poly(D,L-lactide-co-glycolide) nanoparticles (PLGA-NP) and evaluated via IM route in mice. Transmission blocking efficacy of antibodies was evaluated by standard mosquito membrane feeding assay using purified IgG from immune sera. Physicochemical properties and stability of various formulations were evaluated by measuring poly-dispersity index, particle size and zeta potential. Results Mice immunized with CHrPfs25 using alum via IP and IM routes induced comparable immune responses. The highest antibody response was obtained with CHrPfs25 formulated in 4% NE as compared to 8% NE and PLGA-NP. No further increases were observed by combining NE with MPL-A and chitosan. 100% transmission blocking activity was demonstrated at 400 μg/ml of IgG for alum groups (both routes IP and IM), 4% NE and NE-MPL-A. Purified IgG from various adjuvant groups at lower doses (100 μg/mL) still exhibited >90% transmission blocking activity, while 52-81% blocking was seen at 50 μg/mL. Conclusion Results suggest that CHrPfs25 delivered in various adjuvants / nanoparticles elicited strong functional immunogenicity in pre-clinical studies in mice. We are now continuing these studies to develop effective vaccine formulations for further evaluation of immune correlates of relative immunogenicity of CHrPfs25 in various adjuvants and clinical trials. PMID:26113235

  18. A need for better housing to further reduce indoor malaria transmission in areas with high bed net coverage

    PubMed Central

    2013-01-01

    Background The suppression of indoor malaria transmission requires additional interventions that complement the use of insecticide treated nets (ITNs) and indoor residual spraying (IRS). Previous studies have examined the impact of house structure on malaria transmission in areas of low transmission. This study was conducted in a high transmission setting and presents further evidence about the association between specific house characteristics and the abundance of endophilic malaria vectors. Methods Mosquitoes were sampled using CDC light traps from 72 randomly selected houses in two villages on a monthly basis from 2008 to 2011 in rural Southern Tanzania. Generalized linear models using Poisson distributions were used to analyze the association of house characteristics (eave gaps, wall types, roof types, number of windows, rooms and doors, window screens, house size), number of occupants and ITN usage with mean catches of malaria vectors (An.gambiae s.l. and An. funestus). Results A total of 36490 female An. gambiae s.l. were collected in Namwawala village and 21266 in Idete village. As for An. funestus females, 2268 were collected in Namwawala and 3398 in Idete. Individually, each house factor had a statistically significant impact (p < 0.05) on the mean catches for An. gambiae s.l. but not An. funestus. A multivariate analysis indicated that the combined absence or presence of eaves, treated or untreated bed-nets, the number of house occupants, house size, netting over windows, and roof type were significantly related (p < 0.05) to An.gambiae s.l. and An. funestus house entry in both villages. Conclusions Despite significant reductions in vector density and malaria transmission caused by high coverage of ITNs, high numbers of host-seeking malaria vectors are still found indoors due to house designs that favour mosquito entry. In addition to ITNs and IRS, significant efforts should focus on improving house design to prevent mosquito entry and eliminate

  19. Malaria.

    PubMed

    Heck, J E

    1991-03-01

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

  20. Simulation of Malaria Transmission among Households in a Thai Village using Remotely Sensed Parameters

    NASA Technical Reports Server (NTRS)

    Kiang, Richard K.; Adimi, Farida; Zollner, Gabriela E.; Coleman, Russell E.

    2007-01-01

    We have used discrete-event simulation to model the malaria transmission in a Thailand village with approximately 700 residents. Specifically, we model the detailed interactions among the vector life cycle, sporogonic cycle and human infection cycle under the explicit influences of selected extrinsic and intrinsic factors. Some of the meteorological and environmental parameters used in the simulation are derived from Tropical Rainfall Measuring Mission and the Ikonos satellite data. Parameters used in the simulations reflect the realistic condition of the village, including the locations and sizes of the households, ages and estimated immunity of the residents, presence of farm animals, and locations of larval habitats. Larval habitats include the actual locations where larvae were collected and the probable locations based on satellite data. The output of the simulation includes the individual infection status and the quantities normally observed in field studies, such as mosquito biting rates, sporozoite infection rates, gametocyte prevalence and incidence. Simulated transmission under homogeneous environmental condition was compared with that predicted by a SEIR model. Sensitivity of the output with respect to some extrinsic and intrinsic factors was investigated. Results were compared with mosquito vector and human malaria data acquired over 4.5 years (June 1999 - January 2004) in Kong Mong Tha, a remote village in Kanchanaburi Province, western Thailand. The simulation method is useful for testing transmission hypotheses, estimating the efficacy of insecticide applications, assessing the impacts of nonimmune immigrants, and predicting the effects of socioeconomic, environmental and climatic changes.

  1. Malaria transmission in a region of savanna-forest mosaic, Haut-Ogooué, Gabon.

    PubMed

    Elissa, N; Karch, S; Bureau, P; Ollomo, B; Lawoko, M; Yangari, P; Ebang, B; Georges, A J

    1999-03-01

    During the 2 years 1993 to 1995, an entomological survey was carried out in the savanna-forest area of Franceville, Gabon, investigating malaria transmission in one suburban district of Franceville (Akou) and in one rural village (Benguia). The biting rates of the Anopheles vectors were 10 times higher in the rural zone compared to the suburban zone. Anopheles funestus Giles was the predominant species in both zones followed by Anopheles gambiae s.l. Giles. The densities of Anopheles nili Theobald and Anopheles moucheti Evans were very low. In the suburban zone, transmission was maintained throughout the year by An. funestus and An. gambiae s.l., whereas in rural zones the secondary vectors An. nili and An. moucheti were also involved in transmission. Humans in a suburban setting received one infective bite per person every 4 days, whereas in the rural area the infective biting rate was 4 times higher. Considering each vector, the observed entomological inoculation rates (EIRs) were one infective bite per person every 6 and 17 days for An. funestus and An. gambiae s.l., respectively, at Akou. At Benguia, the EIRs were one infective bite per person every 2, 3, 6, and 19 days for the 4 An. funestus, An. gambiae s.l., An. nili, and An. moucheti, respectively. The predominance of An. funestus over An. gambiae s.l. and its high EIR make it the most important malaria vector in this region of Haut-Ogooué.

  2. Ivermectin to reduce malaria transmission: a research agenda for a promising new tool for elimination

    PubMed Central

    2013-01-01

    Background The heterogeneity of malaria transmission makes widespread elimination a difficult goal to achieve. Most of the current vector control measures insufficiently target outdoor transmission. Also, insecticide resistance threatens to diminish the efficacy of the most prevalent measures, indoor residual spray and insecticide treated nets. Innovative approaches are needed. The use of endectocides, such as ivermectin, could be an important new addition to the toolbox of anti-malarial measures. Ivermectin effectively targets outdoor transmission, has a novel mechanism of action that could circumvent resistance and might be distributed over the channels already in place for the control of onchocerciasis and lymphatic filariasis. Methods The previous works involving ivermectin and Anopheles vectors are reviewed and summarized. A review of ivermectin’s safety profile is also provided. Finally three definitive clinical trials are described in detail and proposed as the evidence needed for implementation. Several smaller and specific supportive studies are also proposed. Conclusions The use of ivermectin solves many challenges identified for future vector control strategies. It is an effective and safe endectocide that was approved for human use more than 25 years ago. Recent studies suggest it might become an effective and complementary strategy in malaria elimination and eradication efforts; however, intensive research will be needed to make this a reality. PMID:23647969

  3. Malaria vectors and transmission dynamics in Goulmoun, a rural city in south-western Chad

    PubMed Central

    2009-01-01

    Background Knowledge of some baseline entomological data such as Entomological Inoculation Rates (EIR) is crucially needed to assess the epidemiological impact of malaria control activities directed either against parasites or vectors. In Chad, most published surveys date back to the 1960's. In this study, anopheline species composition and their relation to malaria transmission were investigated in a dry Sudanian savannas area of Chad. Methods A 12-month longitudinal survey was conducted in the irrigated rice-fields area of Goulmoun in south western Chad. Human landing catches were performed each month from July 2006 to June 2007 in three compounds (indoors and outdoors) and pyrethrum spray collections were conducted in July, August and October 2006 in 10 randomly selected rooms. Mosquitoes belonging to the Anopheles gambiae complex and to the An. funestus group were identified by molecular diagnostic tools. Plasmodium falciparum infection and blood meal sources were detected by ELISA. Results Nine anopheline species were collected by the two sampling methods. The most aggressive species were An. arabiensis (51 bites/human/night), An. pharoensis (12.5 b/h/n), An. funestus (1.5 b/h/n) and An. ziemanni (1.3 b/h/n). The circumsporozoite protein rate was 1.4% for An. arabiensis, 1.4% for An. funestus, 0.8% for An. pharoensis and 0.5% for An. ziemanni. Malaria transmission is seasonal, lasting from April to December. However, more than 80% of the total EIR was concentrated in the period from August to October. The overall annual EIR was estimated at 311 bites of infected anophelines/human/year, contributed mostly by An. arabiensis (84.5%) and An. pharoensis (12.2%). Anopheles funestus and An. ziemanni played a minor role. Parasite inoculation occurred mostly after 22:00 hours but around 20% of bites of infected anophelines were distributed earlier in the evening. Conclusion The present study revealed the implication of An. pharoensis in malaria transmission in the

  4. Malaria transmission pattern resilience to climatic variability is mediated by insecticide-treated nets

    PubMed Central

    Chaves, Luis Fernando; Kaneko, Akira; Taleo, George; Pascual, Mercedes; Wilson, Mark L

    2008-01-01

    Background Malaria is an important public-health problem in the archipelago of Vanuatu and climate has been hypothesized as important influence on transmission risk. Beginning in 1988, a major intervention using insecticide-treated bed nets (ITNs) was implemented in the country in an attempt to reduce Plasmodium transmission. To date, no study has addressed the impact of ITN intervention in Vanuatu, how it may have modified the burden of disease, and whether there were any changes in malaria incidence that might be related to climatic drivers. Methods and findings Monthly time series (January 1983 through December 1999) of confirmed Plasmodium falciparum and Plasmodium vivax infections in the archipelago were analysed. During this 17 year period, malaria dynamics underwent a major regime shift around May 1991, following the introduction of bed nets as a control strategy in the country. By February of 1994 disease incidence from both parasites was reduced by at least 50%, when at most 20% of the population at risk was covered by ITNs. Seasonal cycles, as expected, were strongly correlated with temperature patterns, while inter-annual cycles were associated with changes in precipitation. Following the bed net intervention, the influence of environmental drivers of malaria dynamics was reduced by 30–80% for climatic forces, and 33–54% for other factors. A time lag of about five months was observed for the qualitative change ("regime shift") between the two parasites, the change occurring first for P. falciparum. The latter might be explained by interspecific interactions between the two parasites within the human hosts and their distinct biology, since P. vivax can relapse after a primary infection. Conclusion The Vanuatu ITN programme represents an excellent example of implementing an infectious disease control programme. The distribution was undertaken to cover a large, local proportion (~80%) of people in villages where malaria was present. The successful

  5. Evidence for an increased risk of transmission of simian immunodeficiency virus and malaria in a rhesus macaque coinfection model.

    PubMed

    Trott, Kristin A; Chau, Jennifer Y; Hudgens, Michael G; Fine, Jason; Mfalila, Chelu K; Tarara, Ross P; Collins, William E; Sullivan, Joann; Luckhart, Shirley; Abel, Kristina

    2011-11-01

    In sub-Saharan Africa, HIV-1 infection frequently occurs in the context of other coinfecting pathogens, most importantly, Mycobacterium tuberculosis and malaria parasites. The consequences are often devastating, resulting in enhanced morbidity and mortality. Due to the large number of confounding factors influencing pathogenesis in coinfected people, we sought to develop a nonhuman primate model of simian immunodeficiency virus (SIV)-malaria coinfection. In sub-Saharan Africa, Plasmodium falciparum is the most common malaria parasite and is responsible for most malaria-induced deaths. The simian malaria parasite Plasmodium fragile can induce clinical symptoms, including cerebral malaria in rhesus macaques, that resemble those of P. falciparum infection in humans. Thus, based on the well-characterized rhesus macaque model of SIV infection, this study reports the development of a novel rhesus macaque SIV-P. fragile coinfection model to study human HIV-P. falciparum coinfection. Using this model, we show that coinfection is associated with an increased, although transient, risk of both HIV and malaria transmission. Specifically, SIV-P. fragile coinfected macaques experienced an increase in SIV viremia that was temporarily associated with an increase in potential SIV target cells and systemic immune activation during acute parasitemia. Conversely, primary parasitemia in SIV-P. fragile coinfected animals resulted in higher gametocytemia that subsequently translated into higher oocyst development in mosquitoes. To our knowledge, this is the first animal model able to recapitulate the increased transmission risk of both HIV and malaria in coinfected humans. Therefore, this model could serve as an essential tool to elucidate distinct immunological, virological, and/or parasitological parameters underlying disease exacerbation in HIV-malaria coinfected people.

  6. Comparing the impact of artemisinin-based combination therapies on malaria transmission in sub-Saharan Africa.

    PubMed

    Ndeffo Mbah, Martial L; Parikh, Sunil; Galvani, Alison P

    2015-03-01

    Artemisinin-based combination therapies (ACTs) are currently considered the first-line treatments for uncomplicated Plasmodium falciparum malaria. Among these, artemether-lumefantrine (AL) has been the most widely prescribed ACT in sub-Saharan Africa. Recent clinical trials conducted in sub-Saharan Africa have shown that dihydroartemisinin-piperaquine (DP), a most recent ACT, may have a longer post-treatment prophylactic period and post-treatment infection period (duration of gametocyte carriage) than AL. Using epidemiological and clinical data on the efficacy of AL and DP, we developed and parameterized a mathematical transmission model that we used to compare the population-level impact of AL and DP for reducing P. falciparum malaria transmission in sub-Saharan Africa. Our results showed that DP is likely to more effectively reduce malaria incidence of clinical episodes than AL. However in low P. falciparum transmission areas, DP and AL are likely to be equally effective in reducing malaria prevalence. The predictions of our model were shown to be robust to the empirical uncertainty summarizing the epidemiological parameters. DP should be considered as a replacement for AL as first-line treatment of uncomplicated malaria in highly endemic P. falciparum communities. To optimize the effectiveness of ACTs, it is necessary to tailor treatment policies to the transmission intensity in different settings.

  7. Seroprevalence of Antibodies against Plasmodium falciparum Sporozoite Antigens as Predictive Disease Transmission Markers in an Area of Ghana with Seasonal Malaria Transmission

    PubMed Central

    Bosomprah, Samuel; Kyei-Baafour, Eric; Dickson, Emmanuel K.; Tornyigah, Bernard; Angov, Evelina; Dutta, Sheetij; Dodoo, Daniel; Sedegah, Martha; Koram, Kwadwo A.

    2016-01-01

    Introduction As an increasing number of malaria-endemic countries approach the disease elimination phase, sustenance of control efforts and effective monitoring are necessary to ensure success. Mathematical models that estimate anti-parasite antibody seroconversion rates are gaining relevance as more sensitive transmission intensity estimation tools. Models however estimate yearly seroconversion and seroreversion rates and usually predict long term changes in transmission, occurring years before the time of sampling. Another challenge is the identification of appropriate antigen targets since specific antibody levels must directly reflect changes in transmission patterns. We therefore investigated the potential of antibodies to sporozoite and blood stage antigens for detecting short term differences in malaria transmission in two communities in Northern Ghana with marked, seasonal transmission. Methods Cross-sectional surveys were conducted during the rainy and dry seasons in two communities, one in close proximity to an irrigation dam and the other at least 20 Km away from the dam. Antibodies against the sporozoite-specific antigens circumsporozoite protein (CSP) and Cell traversal for ookinetes and sporozoites (CelTOS) and the classical blood stage antigen apical membrane antigen 1 (AMA1) were measured by indirect ELISA. Antibody levels and seroprevalence were compared between surveys and between study communities. Antibody seroprevalence data were fitted to a modified reversible catalytic model to estimate the seroconversion and seroreversion rates. Results Changes in sporozoite-specific antibody levels and seroprevalence directly reflected differences in parasite prevalence between the rainy and dry seasons and hence the extent of malaria transmission. Seroconversion rate estimates from modelled seroprevalence data did not however support the above observation. Conclusions The data confirms the potential utility of sporozoite-specific antigens as useful markers

  8. Investigating the Contribution of Peri-domestic Transmission to Risk of Zoonotic Malaria Infection in Humans

    PubMed Central

    Manin, Benny O.; Ferguson, Heather M.; Vythilingam, Indra; Fornace, Kim; William, Timothy; Torr, Steve J.; Drakeley, Chris; Chua, Tock H.

    2016-01-01

    Background In recent years, the primate malaria Plasmodium knowlesi has emerged in human populations throughout South East Asia, with the largest hotspot being in Sabah, Malaysian Borneo. Control efforts are hindered by limited knowledge of where and when people get exposed to mosquito vectors. It is assumed that exposure occurs primarily when people are working in forest areas, but the role of other potential exposure routes (including domestic or peri-domestic transmission) has not been thoroughly investigated. Methodology/Principal Findings We integrated entomological surveillance within a comprehensive case-control study occurring within a large hotspot of transmission in Sabah, Malaysia. Mosquitoes were collected at 28 pairs households composed of one where an occupant had a confirmed P. knowlesi infection within the preceding 3 weeks (“case”) and an associated “control” where no infection was reported. Human landing catches were conducted to measure the number and diversity of mosquitoes host seeking inside houses and in the surrounding peri-domestic (outdoors but around the household) areas. The predominant malaria vector species was Anopheles balabacensis, most of which were caught outdoors in the early evening (6pm - 9pm). It was significantly more abundant in the peri-domestic area than inside houses (5.5-fold), and also higher at case than control households (0.28±0.194 vs 0.17±0.127, p<0.001). Ten out of 641 An. balabacensis tested were positive for simian malaria parasites, but none for P. knowlesi. Conclusions/Significance This study shows there is a possibility that humans can be exposed to P. knowlesi infection around their homes. The vector is highly exophagic and few were caught indoors indicating interventions using bednets inside households may have relatively little impact. PMID:27741235

  9. Vectors and malaria transmission in deforested, rural communities in north-central Vietnam

    PubMed Central

    2010-01-01

    Background Malaria is still prevalent in rural communities of central Vietnam even though, due to deforestation, the primary vector Anopheles dirus is uncommon. In these situations little is known about the secondary vectors which are responsible for maintaining transmission. Basic information on the identification of the species in these rural communities is required so that transmission parameters, such as ecology, behaviour and vectorial status can be assigned to the appropriate species. Methods In two rural villages - Khe Ngang and Hang Chuon - in Truong Xuan Commune, Quang Binh Province, north central Vietnam, a series of longitudinal entomological surveys were conducted during the wet and dry seasons from 2003 - 2007. In these surveys anopheline mosquitoes were collected in human landing catches, paired human and animal bait collections, and from larval surveys. Specimens belonging to species complexes were identified by PCR and sequence analysis, incrimination of vectors was by detection of circumsporozoite protein using an enzyme-linked immunosorbent assay. Results Over 80% of the anopheline fauna was made up of Anopheles sinensis, Anopheles aconitus, Anopheles harrisoni, Anopheles maculatus, Anopheles sawadwongporni, and Anopheles philippinensis. PCR and sequence analysis resolved identification issues in the Funestus Group, Maculatus Group, Hyrcanus Group and Dirus Complex. Most species were zoophilic and while all species could be collected biting humans significantly higher densities were attracted to cattle and buffalo. Anopheles dirus was the most anthropophilic species but was uncommon making up only 1.24% of all anophelines collected. Anopheles sinensis, An. aconitus, An. harrisoni, An. maculatus, An. sawadwongporni, Anopheles peditaeniatus and An. philippinensis were all found positive for circumsporozoite protein. Heterogeneity in oviposition site preference between species enabled vector densities to be high in both the wet and dry seasons

  10. Maternally supplied S-acyl-transferase is required for crystalloid organelle formation and transmission of the malaria parasite

    PubMed Central

    Duarte, Neuza; Ramesar, Jai; Avramut, M. Cristina; Koster, Abraham J.; Dessens, Johannes T.; Frischknecht, Friedrich; Chevalley-Maurel, Séverine; Janse, Chris J.; Franke-Fayard, Blandine; Mair, Gunnar R.

    2016-01-01

    Transmission of the malaria parasite from the mammalian host to the mosquito vector requires the formation of adequately adapted parasite forms and stage-specific organelles. Here we show that formation of the crystalloid—a unique and short-lived organelle of the Plasmodium ookinete and oocyst stage required for sporogony—is dependent on the precisely timed expression of the S-acyl-transferase DHHC10. DHHC10, translationally repressed in female Plasmodium berghei gametocytes, is activated translationally during ookinete formation, where the protein is essential for the formation of the crystalloid, the correct targeting of crystalloid-resident protein LAP2, and malaria parasite transmission. PMID:27303037

  11. Influence of deltamethrin treatment of bed nets on malaria transmission in the Kou valley, Burkina Faso.

    PubMed Central

    Robert, V.; Carnevale, P.

    1991-01-01

    A 3-year entomological study was carried out on the transmission of malaria in a village of 900 inhabitants in a rice-growing area of Burkina Faso. In the study area inhabitants use bed nets to protect themselves from mosquito bites. In the first year of the study, baseline data were collected; in the second year, the village was divided in two parts and all the bed nets in the southern part were sprayed with deltamethrin (25 mg/m2); and in the third year, all the bed nets in both parts of the village were sprayed. The inoculation rate was estimated by hand collection of mosquitos on human volunteers who were not protected by bed nets. The overall inoculation rate in the first year was 55 infected bites per person and was higher in the southern than in the northern part of the village. During the second year the rate increased to 70 bites per person on average (but was slightly lower than this in the southern part of the village). During the third year, the inoculation rate fell to three infected bites per year, i.e., a reduction of 94% compared with the first year. This reduction arose primarily because of a marked decrease in the sporozoitic index and a lower density of vectors. Thus, use of pyrethroid-impregnated bed nets by all members of the community appears to be a major tool in preventing transmission of malaria. PMID:1786622

  12. Mother-to-Children Plasmodium falciparum Asymptomatic Malaria Transmission at Saint Camille Medical Centre in Ouagadougou, Burkina Faso

    PubMed Central

    Douamba, Zoenabo; Dao, Nangnéré Ginette Laure; Zohoncon, Théodora Mahoukédé; Bisseye, Cyrille; Compaoré, Tegwindé Rebeca; Kafando, Jacques Gilbert; Sombie, Bavouma Charles; Ouermi, Djeneba; Djigma, Florencia W.; Ouedraogo, Paul; Ghilat, Nadine; Colizzi, Vittorio; Simpore, Jacques

    2014-01-01

    Background. Malaria's prevalence during pregnancy varies widely in parts of sub-Saharan Africa, including Burkina Faso. The objective of this study was to evaluate the incidence of mother-to-child malaria transmission during childbirth at St. Camille Medical Centre in the city of Ouagadougou. Methods. Two hundred and thirty-eight (238) women and their newborns were included in the study. Women consenting to participate in this study responded to a questionnaire that identified their demographic characteristics. Asymptomatic malaria infection was assessed by rapid detection test Acon (Acon Malaria Pf, San Diego, USA) and by microscopic examination of Giemsa-stained thick and thin smears from peripheral, placental, and umbilical cord blood. Birth weights were recorded and the biological analyses of mothers and newborns' blood were also performed. Results. The utilization of long-lasting insecticidal nets (LLINs) and intermittent preventive treatment with sulfadoxine-pyrimethamine (SP) were 86.6% and 84.4%, respectively. The parasitic infection rates of 9.5%, 8.9%, and 2.8% were recorded, respectively, for the peripheral, placental, and umbilical cord blood. Placental infection was strongly associated with the presence of parasites in the maternal peripheral blood and a parasite density of >1000 parasites/µL. Conclusion. The prevalence of congenital malaria was reduced but was associated with a high rate of mother-to-child malaria transmission. PMID:25506464

  13. The drug sensitivity and transmission dynamics of human malaria on Nias Island, North Sumatra, Indonesia.

    PubMed

    Fryauff, D J; Leksana, B; Masbar, S; Wiady, I; Sismadi, P; Susanti, A I; Nagesha, H S; Syafruddin; Atmosoedjono, S; Bangs, M J; Baird, J K

    2002-07-01

    Nias Island, off the north-western coast of Sumatra, Indonesia, was one of the first locations in which chloroquine-resistant Plasmodium vivax malaria was reported. This resistance is of particular concern because its ancient megalithic culture and the outstanding surfing conditions make the island a popular tourist destination. International travel to and from the island could rapidly spread chloroquine-resistant strains of P. vivax across the planet. The threat posed by such strains, locally and internationally, has led to the routine and periodic re-assessment of the efficacy of antimalarial drugs and transmission potential on the island. Active case detection identified malaria in 124 (17%) of 710 local residents whereas passive case detection, at the central health clinic, confirmed malaria in 77 (44%) of 173 cases of presumed 'clinical malaria'. Informed consenting volunteers who had malarial parasitaemias were treated, according to the Indonesian Ministry of Health's recommendations, with sulfadoxine-pyrimethamine (SP) on day 0 (for P. falciparum) or with chloroquine (CQ) on days 0, 1 and 2 (for P. vivax). Each volunteer was then monitored for clinical and parasite response until day 28. Recurrent parasitaemia by day 28 treatment was seen in 29 (83%) of the 35 P. falciparum cases given SP (14, 11 and four cases showing RI, RII and RIII resistance, respectively). Recurrent parasitaemia was also observed, between day 11 and day 21, in six (21%) of the 28 P. vivax cases given CQ. Although the results of quantitative analysis confirmed only low prevalences of CQ-resistant P. vivax malaria, the prevalence of SP resistance among the P. falciparum cases was among the highest seen in Indonesia. When the parasites present in the volunteers with P. falciparum infections were genotyped, mutations associated with pyrimethamine resistance were found at high frequency in the dhfr gene but there was no evidence of selection for sulfadoxine resistance in the dhps gene

  14. Assessing malaria transmission in a low endemicity area of north-western Peru

    PubMed Central

    2013-01-01

    Background Where malaria endemicity is low, control programmes need increasingly sensitive tools for monitoring malaria transmission intensity (MTI) and to better define health priorities. A cross-sectional survey was conducted in a low endemicity area of the Peruvian north-western coast to assess the MTI using both molecular and serological tools. Methods Epidemiological, parasitological and serological data were collected from 2,667 individuals in three settlements of Bellavista district, in May 2010. Parasite infection was detected using microscopy and polymerase chain reaction (PCR). Antibodies to Plasmodium vivax merozoite surface protein-119 (PvMSP119) and to Plasmodium falciparum glutamate-rich protein (PfGLURP) were detected by ELISA. Risk factors for exposure to malaria (seropositivity) were assessed by multivariate survey logistic regression models. Age-specific antibody prevalence of both P. falciparum and P. vivax were analysed using a previously published catalytic conversion model based on maximum likelihood for generating seroconversion rates (SCR). Results The overall parasite prevalence by microscopy and PCR were extremely low: 0.3 and 0.9%, respectively for P. vivax, and 0 and 0.04%, respectively for P. falciparum, while seroprevalence was much higher, 13.6% for P. vivax and 9.8% for P. falciparum. Settlement, age and occupation as moto-taxi driver during previous year were significantly associated with P. falciparum exposure, while age and distance to the water drain were associated with P. vivax exposure. Likelihood ratio tests supported age seroprevalence curves with two SCR for both P. vivax and P. falciparum indicating significant changes in the MTI over time. The SCR for PfGLURP was 19-fold lower after 2002 as compared to before (λ1 = 0.022 versus λ2 = 0.431), and the SCR for PvMSP119 was four-fold higher after 2006 as compared to before (λ1 = 0.024 versus λ2 = 0.006). Conclusion Combining molecular and serological tools

  15. Plasmodium yoelii nigeriensis (N67) Is a Robust Animal Model to Study Malaria Transmission by South American Anopheline Mosquitoes

    PubMed Central

    Molina-Cruz, Alvaro; Pimenta, Paulo F.; Barillas-Mury, Carolina

    2016-01-01

    Malaria is endemic in the American continent and the Amazonian rainforest is the region with the highest risk of transmission. However, the lack of suitable experimental models to infect malaria vectors from the Americas has limited the progress to understand the biology of transmission in this region. Anopheles aquasalis, a major vector in coastal areas of South America, was found to be highly refractory to infection with two strains of Plasmodium falciparum (NF54 and 7G8) and with Plasmodium berghei (mouse malaria), even when the microbiota was eliminated with antibiotics and oxidative stress was reduced with uric acid. In contrast, An. aquasalis females treated with antibiotics and uric acid are susceptible to infection with a second murine parasite, Plasmodium yoelii nigeriensis N67 (PyN67). Anopheles albimanus, one of the main malaria vectors in Central America, Southern Mexico and the Caribbean, was more susceptible to infection with PyN67 than An. aquasalis, even in the absence of any pre-treatment, but was still less susceptible than Anopheles stephensi. Disruption of the complement-like system in An. albimanus significantly enhanced PyN67 infection, indicating that the mosquito immune system is mounting effective antiplasmodial responses. PyN67 has the ability to infect a broad range of anophelines and is an excellent model to study malaria transmission by South American vectors. PMID:27911924

  16. The multiplicity of malaria transmission: a review of entomological inoculation rate measurements and methods across sub-Saharan Africa

    PubMed Central

    Kelly-Hope, Louise A; McKenzie, F Ellis

    2009-01-01

    Plasmodium falciparum malaria is a serious tropical disease that causes more than one million deaths each year, most of them in Africa. It is transmitted by a range of Anopheles mosquitoes and the risk of disease varies greatly across the continent. The "entomological inoculation rate" is the commonly-used measure of the intensity of malaria transmission, yet the methods used are currently not standardized, nor do they take the ecological, demographic, and socioeconomic differences across populations into account. To better understand the multiplicity of malaria transmission, this study examines the distribution of transmission intensity across sub-Saharan Africa, reviews the range of methods used, and explores ecological parameters in selected locations. It builds on an extensive geo-referenced database and uses geographical information systems to highlight transmission patterns, knowledge gaps, trends and changes in methodologies over time, and key differences between land use, population density, climate, and the main mosquito species. The aim is to improve the methods of measuring malaria transmission, to help develop the way forward so that we can better assess the impact of the large-scale intervention programmes, and rapid demographic and environmental change taking place across Africa. PMID:19166589

  17. The multiplicity of malaria transmission: a review of entomological inoculation rate measurements and methods across sub-Saharan Africa.

    PubMed

    Kelly-Hope, Louise A; McKenzie, F Ellis

    2009-01-23

    Plasmodium falciparum malaria is a serious tropical disease that causes more than one million deaths each year, most of them in Africa. It is transmitted by a range of Anopheles mosquitoes and the risk of disease varies greatly across the continent. The "entomological inoculation rate" is the commonly-used measure of the intensity of malaria transmission, yet the methods used are currently not standardized, nor do they take the ecological, demographic, and socioeconomic differences across populations into account. To better understand the multiplicity of malaria transmission, this study examines the distribution of transmission intensity across sub-Saharan Africa, reviews the range of methods used, and explores ecological parameters in selected locations. It builds on an extensive geo-referenced database and uses geographical information systems to highlight transmission patterns, knowledge gaps, trends and changes in methodologies over time, and key differences between land use, population density, climate, and the main mosquito species. The aim is to improve the methods of measuring malaria transmission, to help develop the way forward so that we can better assess the impact of the large-scale intervention programmes, and rapid demographic and environmental change taking place across Africa.

  18. Genetic diversity of transmission-blocking vaccine candidates Pvs25 and Pvs28 in Plasmodium vivax isolates from Yunnan Province, China

    PubMed Central

    2011-01-01

    Background Transmission-blocking vaccines (TBVs) have been considered an important strategy for disrupting the malaria transmission cycle, especially for Plasmodium vivax malaria, which undergoes gametocytogenesis earlier during infection. Pvs25 and Pvs28 are transmission-blocking vaccine candidates for P. vivax malaria. Assessment of genetic diversity of the vaccine candidates will provide necessary information for predicting the performance of vaccines, which will guide us during the development of malaria vaccines. Results We sequenced the coding regions of pvs25 and pvs28 from 30 P. vivax isolates from Yunnan Province, identifying five amino acid haplotypes of Pvs25 and seven amino acid haplotypes of Pvs28. Among a total of four mutant residues, the predominant haplotype of Pvs25 only had the I130T substitution. For Pvs28, a total of eight amino acid substitutions were identified. The predominant haplotype of Pvs28 had two substitution at positions 52 (M52L) and 140 (T140S) with 5-6 GSGGE/D tandem repeats at the end of fourth EGF-like domain. Most amino acid substitutions were common with previous reports from South Asian isolates. Although the nucleotide diversity of pvs28 (π = 0.0034 ± 0.0012) was significantly higher than pvs25 (π = 0.0013 ± 0.0009), it was still conserved when compared with the blood stage vaccine candidates. Conclusions Genetic analysis revealed limited genetic diversity of pvs25 and pvs28, suggesting antigenic diversity may not be a particular problem for Sal I based TBVs in most P. vivax-endemic areas of China. PMID:22117620

  19. Factors affecting treatment-seeking for febrile illness in a malaria endemic block in Boudh district, Orissa, India: policy implications for malaria control

    PubMed Central

    2010-01-01

    Background Orissa state in eastern India accounts for the highest malaria burden to the nation. However, evidences are limited on its treatment-seeking behaviour in the state. We assessed the treatment-seeking behaviour towards febrile illness in a malaria endemic district in Orissa. Methods A cross-sectional community-based survey was carried out during the high malaria transmission season of 2006 in Boudh district. Respondents (n = 300) who had fever with chills within two weeks prior to the day of data collection were selected through a multi-stage sampling and interviewed with a pre-tested and structured interview schedule. Malaria treatment providers (n = 23) were interviewed in the district to gather their insights on factors associated with prompt and effective treatment through a semi-structured and open-ended interview guideline. Results Majority of respondents (n = 281) sought some sort of treatment e.g. government health facility (35.7%), less qualified providers (31.3%), and community level health workers and volunteers (24.3%). The single most common reason (66.9%) for choosing a provider was proximity. Over a half (55.7%) sought treatment from appropriate providers within 48 hours of onset of symptoms. Respondents under five years (OR 2.00, 95% CI 0.84-4.80, P = 0.012), belonging to scheduled tribe community (OR 2.13, 95% CI 1.11-4.07, P = 0.022) and visiting a provider more than five kilometers (OR 2.04, 95% CI 1.09-3.83, P = 0.026) were more likely to have delayed or inappropriate treatment. Interviews with the providers indicated that patients' lack of trust in community volunteers providing treatment led to inappropriate treatment-seeking from the less qualified providers. The reasons for the lack of trust included drug side effects, suspicions about drug quality, stock-outs of drugs and inappropriate attitude of the provider. Conclusion Large-scale involvement of less qualified providers is suggested in the malaria control programme as volunteers

  20. High effective coverage of vector control interventions in children after achieving low malaria transmission in Zanzibar, Tanzania

    PubMed Central

    2013-01-01

    Background Formerly a high malaria transmission area, Zanzibar is now targeting malaria elimination. A major challenge is to avoid resurgence of malaria, the success of which includes maintaining high effective coverage of vector control interventions such as bed nets and indoor residual spraying (IRS). In this study, caretakers' continued use of preventive measures for their children is evaluated, following a sharp reduction in malaria transmission. Methods A cross-sectional community-based survey was conducted in June 2009 in North A and Micheweni districts in Zanzibar. Households were randomly selected using two-stage cluster sampling. Interviews were conducted with 560 caretakers of under-five-year old children, who were asked about perceptions on the malaria situation, vector control, household assets, and intention for continued use of vector control as malaria burden further decreases. Results Effective coverage of vector control interventions for under-five children remains high, although most caretakers (65%; 363/560) did not perceive malaria as presently being a major health issue. Seventy percent (447/643) of the under-five children slept under a long-lasting insecticidal net (LLIN) and 94% (607/643) were living in houses targeted with IRS. In total, 98% (628/643) of the children were covered by at least one of the vector control interventions. Seasonal bed-net use for children was reported by 25% (125/508) of caretakers of children who used bed nets. A high proportion of caretakers (95%; 500/524) stated that they intended to continue using preventive measures for their under-five children as malaria burden further reduces. Malaria risk perceptions and different perceptions of vector control were not found to be significantly associated with LLIN effective coverage. Conclusions While the majority of caretakers felt that malaria had been reduced in Zanzibar, effective coverage of vector control interventions remained high. Caretakers appreciated the

  1. [Role of Anopheles melas Theobald (1903) on malaria transmission in a mangrove swamp in Saloum (Senegal)].

    PubMed

    Diop, A; Molez, J F; Konaté, L; Fontenille, D; Gaye, O; Diouf, M; Diagne, M; Faye, O

    2002-09-01

    From June 1995 to January 1998, entomological studies carried out in five villages located in the Delta's Saloum have allowed to better understand the contribution of An. melas Theobald (1903) to malaria transmission in mangrove swamp. Among the five villages studied, three of them (Simal, Djilor and Marlothie) located along the Saloum river, are colonised by An. arabiensis; the two others (Djifere and Diakhanor) located between the sea and the river, are colonised by An. melas. During the rainy season and at the beginning of the dry season, An. melas and An. arabiensis are sympatric. The ratio of An. melas/An. arabiensis increases when we go closer the coast where An. melas becomes quite exclusive. When An. melas is predominant, endophagy, endophily and anthropophily are very marked. The parturity rates are lower in An. melas than in An. arabiensis. In the predominance area of each species, transmission is on the same level. During the period of sympatry, An. arabiensis is responsible for the transmission and when it is absent, An. melas carries on. Transmission occurs from July to March with a maximum at the beginning of the dry season. In the villages of the mangrove swamp, its prolongation until the middle of the dry season is due to An. melas.

  2. Low and seasonal malaria transmission in the middle Senegal River basin: identification and characteristics of Anopheles vectors

    PubMed Central

    2012-01-01

    Background During the last decades two dams were constructed along the Senegal River. These intensified the practice of agriculture along the river valley basin. We conducted a study to assess malaria vector diversity, dynamics and malaria transmission in the area. Methods A cross-sectional entomological study was performed in September 2008 in 20 villages of the middle Senegal River valley to evaluate the variations of Anopheles density according to local environment. A longitudinal study was performed, from October 2008 to January 2010, in 5 selected villages, to study seasonal variations of malaria transmission. Results Among malaria vectors, 72.34% of specimens collected were An. arabiensis, 5.28% An. gambiae of the S molecular form, 3.26% M form, 12.90% An. pharoensis, 4.70% An. ziemanni, 1.48% An. funestus and 0.04% An. wellcomei. Anopheles density varied according to village location. It ranged from 0 to 21.4 Anopheles/room/day and was significantly correlated with the distance to the nearest ditch water but not to the river. Seasonal variations of Anopheles density and variety were observed with higher human biting rates during the rainy season (8.28 and 7.55 Anopheles bite/man/night in October 2008 and 2009 respectively). Transmission was low and limited to the rainy season (0.05 and 0.06 infected bite/man/night in October 2008 and 2009 respectively). During the rainy season, the endophagous rate was lower, the anthropophagic rate higher and L1014F kdr frequency higher. Conclusions Malaria vectors are present at low-moderate density in the middle Senegal River basin with An. arabiensis as the predominant species. Other potential vectors are An. gambiae M and S form and An. funestus. Nonetheless, malaria transmission was extremely low and seasonal. PMID:22269038

  3. Predicting key malaria transmission factors, biting and entomological inoculation rates, using modelled soil moisture in Kenya.

    PubMed

    Patz, J A; Strzepek, K; Lele, S; Hedden, M; Greene, S; Noden, B; Hay, S I; Kalkstein, L; Beier, J C

    1998-10-01

    While malaria transmission varies seasonally, large inter-annual heterogeneity of malaria incidence occurs. Variability in entomological parameters, biting rates and entomological inoculation rates (EIR) have been strongly associated with attack rates in children. The goal of this study was to assess the weather's impact on weekly biting and EIR in the endemic area of Kisian, Kenya. Entomological data collected by the U.S. Army from March 1986 through June 1988 at Kisian, Kenya was analysed with concurrent weather data from nearby Kisumu airport. A soil moisture model of surface-water availability was used to combine multiple weather parameters with landcover and soil features to improve disease prediction. Modelling soil moisture substantially improved prediction of biting rates compared to rainfall; soil moisture lagged two weeks explained up to 45% of An. gambiae biting variability, compared to 8% for raw precipitation. For An. funestus, soil moisture explained 32% variability, peaking after a 4-week lag. The interspecies difference in response to soil moisture was significant (P < 0.00001). A satellite normalized differential vegetation index (NDVI) of the study site yielded a similar correlation (r = 0.42 An. gambiae). Modelled soil moisture accounted for up to 56% variability of An. gambiae EIR, peaking at a lag of six weeks. The relationship between temperature and An. gambiae biting rates was less robust; maximum temperature r2 = -0.20, and minimum temperature r2 = 0.12 after lagging one week. Benefits of hydrological modelling are compared to raw weather parameters and to satellite NDVI. These findings can improve both current malaria risk assessments and those based on El Niño forecasts or global climate change model projections.

  4. Remote Sensing as a Landscape Epidemiologic Tool to Identify Villages at High Risk for Malaria Transmission

    NASA Technical Reports Server (NTRS)

    Beck, Louisa R.; Rodriquez, Mario H.; Dister, Sheri W.; Rodriquez, Americo D.; Rejmankova, Eliska; Ulloa, Armando; Meza, Rosa A.; Roberts, Donald R.; Paris, Jack F.; Spanner, Michael A.; Washino, Robert K.; Hacker, Carl; Legters, Llewellyn F.

    1994-01-01

    A landscape approach using remote sensing and Geographic Information System (GIS) technologies was developed to discriminate between villages at high and low risk for malaria transmission, as defined by adult Anopheles albimanus abundance. Satellite data for an area in southern Chiapas, Mexico were digitally processed to generate a map of landscape elements. The GIS processes were used to determine the proportion of mapped landscape elements surrounding 40 villages where An. albimanus data had been collected. The relationships between vector abundance and landscape element proportions were investigated using stepwise discriminant analysis and stepwise linear regression. Both analyses indicated that the most important landscape elements in terms of explaining vector abundance were transitional swamp and unmanaged pasture. Discriminant functions generated for these two elements were able to correctly distinguish between villages with high ind low vector abundance, with an overall accuracy of 90%. Regression results found both transitional swamp and unmanaged pasture proportions to be predictive of vector abundance during the mid-to-late wet season. This approach, which integrates remotely sensed data and GIS capabilities to identify villages with high vector-human contact risk, provides a promising tool for malaria surveillance programs that depend on labor-intensive field techniques. This is particularly relevant in areas where the lack of accurate surveillance capabilities may result in no malaria control action when, in fact, directed action is necessary. In general, this landscape approach could be applied to other vector-borne diseases in areas where: 1. the landscape elements critical to vector survival are known and 2. these elements can be detected at remote sensing scales.

  5. The Plasmodium palmitoyl-S-acyl-transferase DHHC2 is essential for ookinete morphogenesis and malaria transmission

    PubMed Central

    Santos, Jorge M.; Kehrer, Jessica; Franke-Fayard, Blandine; Frischknecht, Friedrich; Janse, Chris J.; Mair, Gunnar R.

    2015-01-01

    The post-translational addition of C-16 long chain fatty acids to protein cysteine residues is catalysed by palmitoyl-S-acyl-transferases (PAT) and affects the affinity of a modified protein for membranes and therefore its subcellular localisation. In apicomplexan parasites this reversible protein modification regulates numerous biological processes and specifically affects cell motility, and invasion of host cells by Plasmodium falciparum merozoites and Toxoplasma gondii tachyzoites. Using inhibitor studies we show here that palmitoylation is key to transformation of zygotes into ookinetes during initial mosquito infection with P. berghei. We identify DHHC2 as a unique PAT mediating ookinete formation and morphogenesis. Essential for life cycle progression in asexual blood stage parasites and thus refractory to gene deletion analyses, we used promoter swap (ps) methodology to maintain dhhc2 expression in asexual blood stages but down regulate expression in sexual stage parasites and during post-fertilization development of the zygote. The ps mutant showed normal gamete formation, fertilisation and DNA replication to tetraploid cells, but was characterised by a complete block in post-fertilisation development and ookinete formation. Our report highlights the crucial nature of the DHHC2 palmitoyl-S-acyltransferase for transmission of the malaria parasite to the mosquito vector through its essential role for ookinete morphogenesis. PMID:26526684

  6. Safety and Reproducibility of a Clinical Trial System Using Induced Blood Stage Plasmodium vivax Infection and Its Potential as a Model to Evaluate Malaria Transmission

    PubMed Central

    Elliott, Suzanne; Sekuloski, Silvana; Sikulu, Maggy; Hugo, Leon; Khoury, David; Cromer, Deborah; Davenport, Miles; Sattabongkot, Jetsumon; Ivinson, Karen; Ockenhouse, Christian; McCarthy, James

    2016-01-01

    Background Interventions to interrupt transmission of malaria from humans to mosquitoes represent an appealing approach to assist malaria elimination. A limitation has been the lack of systems to test the efficacy of such interventions before proceeding to efficacy trials in the field. We have previously demonstrated the feasibility of induced blood stage malaria (IBSM) infection with Plasmodium vivax. In this study, we report further validation of the IBSM model, and its evaluation for assessment of transmission of P. vivax to Anopheles stephensi mosquitoes. Methods Six healthy subjects (three cohorts, n = 2 per cohort) were infected with P. vivax by inoculation with parasitized erythrocytes. Parasite growth was monitored by quantitative PCR, and gametocytemia by quantitative reverse transcriptase PCR (qRT-PCR) for the mRNA pvs25. Parasite multiplication rate (PMR) and size of inoculum were calculated by linear regression. Mosquito transmission studies were undertaken by direct and membrane feeding assays over 3 days prior to commencement of antimalarial treatment, and midguts of blood fed mosquitoes dissected and checked for presence of oocysts after 7–9 days. Results The clinical course and parasitemia were consistent across cohorts, with all subjects developing mild to moderate symptoms of malaria. No serious adverse events were reported. Asymptomatic elevated liver function tests were detected in four of six subjects; these resolved without treatment. Direct feeding of mosquitoes was well tolerated. The estimated PMR was 9.9 fold per cycle. Low prevalence of mosquito infection was observed (1.8%; n = 32/1801) from both direct (4.5%; n = 20/411) and membrane (0.9%; n = 12/1360) feeds. Conclusion The P. vivax IBSM model proved safe and reliable. The clinical course and PMR were reproducible when compared with the previous study using this model. The IBSM model presented in this report shows promise as a system to test transmission-blocking interventions

  7. Shifts in malaria vector species composition and transmission dynamics along the Kenyan coast over the past 20 years

    PubMed Central

    2013-01-01

    Background Over the past 20 years, numerous studies have investigated the ecology and behaviour of malaria vectors and Plasmodium falciparum malaria transmission on the coast of Kenya. Substantial progress has been made to control vector populations and reduce high malaria prevalence and severe disease. The goal of this paper was to examine trends over the past 20 years in Anopheles species composition, density, blood-feeding behaviour, and P. falciparum sporozoite transmission along the coast of Kenya. Methods Using data collected from 1990 to 2010, vector density, species composition, blood-feeding patterns, and malaria transmission intensity was examined along the Kenyan coast. Mosquitoes were identified to species, based on morphological characteristics and DNA extracted from Anopheles gambiae for amplification. Using negative binomial generalized estimating equations, mosquito abundance over the period were modelled while adjusting for season. A multiple logistic regression model was used to analyse the sporozoite rates. Results Results show that in some areas along the Kenyan coast, Anopheles arabiensis and Anopheles merus have replaced An. gambiae sensu stricto (s.s.) and Anopheles funestus as the major mosquito species. Further, there has been a shift from human to animal feeding for both An. gambiae sensu lato (s.l.) (99% to 16%) and An. funestus (100% to 3%), and P. falciparum sporozoite rates have significantly declined over the last 20 years, with the lowest sporozoite rates being observed in 2007 (0.19%) and 2008 (0.34%). There has been, on average, a significant reduction in the abundance of An. gambiae s.l. over the years (IRR = 0.94, 95% CI 0.90–0.98), with the density standing at low levels of an average 0.006 mosquitoes/house in the year 2010. Conclusion Reductions in the densities of the major malaria vectors and a shift from human to animal feeding have contributed to the decreased burden of malaria along the Kenyan coast. Vector species

  8. Anti-Plasmodium falciparum invasion ligand antibodies in a low malaria transmission region, Loreto, Peru

    PubMed Central

    2012-01-01

    Background Erythrocyte invasion by Plasmodium falciparum is a complex process that involves two families; Erythrocyte Binding-Like (EBL) and the Reticulocyte Binding-Like (PfRh) proteins. Antibodies that inhibit merozoite attachment and invasion are believed to be important in mediating naturally acquired immunity and immunity generated by parasite blood stage vaccine candidates. The hypotheses tested in this study were 1) that antibody responses against specific P. falciparum invasion ligands (EBL and PfRh) differ between symptomatic and asymptomatic individuals living in the low-transmission region of the Peruvian Amazon and 2), such antibody responses might have an association, either direct or indirect, with clinical immunity observed in asymptomatically parasitaemic individuals. Methods ELISA was used to assess antibody responses (IgG, IgG1 and IgG3) against recombinant P. falciparum invasion ligands of the EBL (EBA-175, EBA-181, EBA-140) and PfRh families (PfRh1, PfRh2a, PfRh2b, PfRh4 and PfRh5) in 45 individuals infected with P. falciparum from Peruvian Amazon. Individuals were classified as having symptomatic malaria (N=37) or asymptomatic infection (N=8). Results Antibody responses against both EBL and PfRh family proteins were significantly higher in asymptomatic compared to symptomatic individuals, demonstrating an association with clinical immunity. Significant differences in the total IgG responses were observed with EBA-175, EBA-181, PfRh2b, and MSP119 (as a control). IgG1 responses against EBA-181, PfRh2a and PfRh2b were significantly higher in the asymptomatic individuals. Total IgG antibody responses against PfRh1, PfRh2a, PfRh2b, PfRh5, EBA-175, EBA-181 and MSP119 proteins were negatively correlated with level of parasitaemia. IgG1 responses against EBA-181, PfRh2a and PfRh2b and IgG3 response for PfRh2a were also negatively correlated with parasitaemia. Conclusions These data suggest that falciparum malaria patients who develop clinical immunity

  9. [Transmission of malaria in villages far away or situated on the border of a mangrove in Senegal].

    PubMed

    Faye, O; Gaye, O; Faye, O; Diallo, S

    1994-01-01

    During 23 months period, entomological surveys were carried out in three villages of a mangrove area and two others far of the mangrove in the south part of Senegal. An. gambiae s.s was the main malaria vector and the sampling of its population was done by human baits catch. The An. gambiae density was important in the rainy season and the malaria transmission occurred from July to November; the inoculation rate rose from 0 to 123 infected bites per man. Marked yearly and local variations of the transmission intensity were observed. The transmission intensity was higher in the villages far of the mangrove than in those near. The variations of the transmission intensity were related to the larval breeding sites and to the longevity of the An. gambiae females.

  10. Contrasting Transmission Dynamics of Co-endemic Plasmodium vivax and P. falciparum: Implications for Malaria Control and Elimination

    PubMed Central

    Noviyanti, Rintis; Coutrier, Farah; Utami, Retno A. S.; Trimarsanto, Hidayat; Tirta, Yusrifar K.; Trianty, Leily; Kusuma, Andreas; Sutanto, Inge; Kosasih, Ayleen; Kusriastuti, Rita; Hawley, William A.; Laihad, Ferdinand; Lobo, Neil; Marfurt, Jutta; Clark, Taane G.; Price, Ric N.; Auburn, Sarah

    2015-01-01

    Background Outside of Africa, P. falciparum and P. vivax usually coexist. In such co-endemic regions, successful malaria control programs have a greater impact on reducing falciparum malaria, resulting in P. vivax becoming the predominant species of infection. Adding to the challenges of elimination, the dormant liver stage complicates efforts to monitor the impact of ongoing interventions against P. vivax. We investigated molecular approaches to inform the respective transmission dynamics of P. falciparum and P. vivax and how these could help to prioritize public health interventions. Methodology/ Principal Findings Genotype data generated at 8 and 9 microsatellite loci were analysed in 168 P. falciparum and 166 P. vivax isolates, respectively, from four co-endemic sites in Indonesia (Bangka, Kalimantan, Sumba and West Timor). Measures of diversity, linkage disequilibrium (LD) and population structure were used to gauge the transmission dynamics of each species in each setting. Marked differences were observed in the diversity and population structure of P. vivax versus P. falciparum. In Bangka, Kalimantan and Timor, P. falciparum diversity was low, and LD patterns were consistent with unstable, epidemic transmission, amenable to targeted intervention. In contrast, P. vivax diversity was higher and transmission appeared more stable. Population differentiation was lower in P. vivax versus P. falciparum, suggesting that the hypnozoite reservoir might play an important role in sustaining local transmission and facilitating the spread of P. vivax infections in different endemic settings. P. vivax polyclonality varied with local endemicity, demonstrating potential utility in informing on transmission intensity in this species. Conclusions/ Significance Molecular approaches can provide important information on malaria transmission that is not readily available from traditional epidemiological measures. Elucidation of the transmission dynamics circulating in a given

  11. Mapping and predicting malaria transmission in the People's Republic of China, using integrated biology-driven and statistical models.

    PubMed

    Yang, Guo-Jing; Gao, Qi; Zhou, Shui-Sen; Malone, John B; McCarroll, Jennifer C; Tanner, Marcel; Vounatsou, Penelope; Bergquist, Robert; Utzinger, Jürg; Zhou, Xiao-Nong

    2010-11-01

    The purpose of this study was to deepen our understanding of Plasmodium vivax malaria transmission patterns in the People's Republic of China (P.R. China). An integrated modeling approach was employed, combining biological and statistical models. A Delphi approach was used to determine environmental factors that govern malaria transmission. Key factors identified (i.e. temperature, rainfall and relative humidity) were utilized for subsequent mapping and modeling purposes. Yearly growing degree days, annual rainfall and effective yearly relative humidity were extracted from a 15-year time series (1981-1995) of daily environmental data readily available for 676 locations in P.R. China. A suite of eight multinomial regression models, ranging from the null model to a fully saturated one were constructed. Two different information criteria were used for model ranking, namely the corrected Akaike's information criterion and the Bayesian information criterion. Mapping was based on model output data, facilitated by using ArcGIS software. Temperature was found to be the most important environmental factor, followed by rainfall and relative humidity in the Delphi evaluation. However, relative humidity was found to be more important than rainfall and temperature in the ranking list according to the three single environmental factor regression models. We conclude that the distribution of the mosquito vector is mainly related to relative humidity, which thus determines the extent of malaria transmission. However, in regions with relative humidity >60%, temperature is the major driver of malaria transmission intensity. By integrating biology-driven models with statistical regression models, reliable risk maps indicating the distribution of transmission and the intensity can be produced. In a next step, we propose to integrate social and health systems factors into our modeling approach, which should provide a platform for rigorous surveillance and monitoring progress towards P

  12. Anthropophilic mosquitoes and malaria transmission in the eastern foothills of the central highlands of Madagascar.

    PubMed

    Andrianaivolambo, Lala; Domarle, Olivier; Randrianarivelojosia, Milijaona; Ratovonjato, Jocelyn; Le Goff, Gilbert; Talman, Arthur; Ariey, Frédéric; Robert, Vincent

    2010-12-01

    Malaria remains a major public health problem in Madagascar, as it is the first cause of morbidity in health care facilities. Its transmission remains poorly documented. An entomological study was carried out over 1 year (October 2003-September 2004) in Saharevo, a village located at an altitude of 900m on the eastern edge of the Malagasy central highlands. Mosquitoes were sampled weekly upon landing on human volunteers and in various resting-places. Out of 5515 mosquitoes collected on humans, 3219 (58.4%) were anophelines. Eleven anopheline species were represented, among which Anopheles funestus, Anopheles gambiae, Anopheles arabiensis and Anopheles mascarensis. Out of 677 mosquitoes collected in bedrooms by pyrethrum spray catches and in Muirhead-Thomson pits, 656 (96.9%) were anopheline belonging to these four latter species. The proportion of mosquitoes that fed on human varied according to the resting-places and the mosquito species: 86% of An. funestus resting in bedrooms fed on humans, whereas only 16% of An. funestus and 0% of An. mascarensis resting in pits fed on humans. The proportion of anopheline mosquitoes infected with human Plasmodium was measured by circumsporozoite protein-ELISA: 10/633 An. funestus (1.58%), 1/211 An. gambiae s.l. (0.48%) and 2/268 An. mascarensis (0.75%). The annual entomological inoculation rate (number of bites of infected anophelines per adult) was estimated at 2.78. The transmission was mainly due to An. funestus and only observed in the second half of the rainy season, from February to May. These results are discussed in the context of the current malaria vector control policy in Madagascar.

  13. Global analysis of a delayed vector-bias model for malaria transmission with incubation period in mosquitoes.

    PubMed

    Vargas-De-León, Cruz

    2012-01-01

    A delayed vector-bias model for malaria transmission with incubation period in mosquitoes is studied. The delay t corresponds to the time necessary for a latently infected vector to become an infectious vector. We prove that the global stability is completely determined by the threshold parameter, R₀(τ). If R₀(τ) ≥ 1, the disease-free equilibrium is globally asymptotically stable. If R₀(τ) > 1 a unique endemic equilibrium exists and is globally asymptotically stable. We apply our results to Ross-MacDonald malaria models with an incubation period (extrinsic or intrinsic).

  14. A malaria vaccine based on the polymorphic block 2 region of MSP-1 that elicits a broad serotype-spanning immune response.

    PubMed

    Cowan, Graeme J M; Creasey, Alison M; Dhanasarnsombut, Kelwalin; Thomas, Alan W; Remarque, Edmond J; Cavanagh, David R

    2011-01-01

    Polymorphic parasite antigens are known targets of protective immunity to malaria, but this antigenic variation poses challenges to vaccine development. A synthetic MSP-1 Block 2 construct, based on all polymorphic variants found in natural Plasmodium falciparum isolates has been designed, combined with the relatively conserved Block 1 sequence of MSP-1 and expressed in E.coli. The MSP-1 Hybrid antigen has been produced with high yield by fed-batch fermentation and purified without the aid of affinity tags resulting in a pure and extremely thermostable antigen preparation. MSP-1 hybrid is immunogenic in experimental animals using adjuvants suitable for human use, eliciting antibodies against epitopes from all three Block 2 serotypes. Human serum antibodies from Africans naturally exposed to malaria reacted to the MSP-1 hybrid as strongly as, or better than the same serum reactivities to individual MSP-1 Block 2 antigens, and these antibody responses showed clear associations with reduced incidence of malaria episodes. The MSP-1 hybrid is designed to induce a protective antibody response to the highly polymorphic Block 2 region of MSP-1, enhancing the repertoire of MSP-1 Block 2 antibody responses found among immune and semi-immune individuals in malaria endemic areas. The target population for such a vaccine is young children and vulnerable adults, to accelerate the acquisition of a full range of malaria protective antibodies against this polymorphic parasite antigen.

  15. Melanotic Pathology and Vertical Transmission of the Gut Commensal Elizabethkingia meningoseptica in the Major Malaria Vector Anopheles gambiae

    PubMed Central

    Christophides, Georges K.

    2013-01-01

    Background The resident gut flora is known to have significant impacts on the life history of the host organism. Endosymbiotic bacterial species in the Anopheles mosquito gut are potent modulators of sexual development of the malaria parasite, Plasmodium, and thus proposed as potential control agents of malaria transmission. Results Here we report a melanotic pathology in the major African malaria vector Anopheles gambiae, caused by the dominant mosquito endosymbiont Elizabethkingiameningoseptica. Transfer of melanised tissues into the haemolymph of healthy adult mosquitoes or direct haemolymph inoculation with isolated E. meningoseptica bacteria were the only means for transmission and de novo formation of melanotic lesions, specifically in the fat body tissues of recipient individuals. We show that E. meningoseptica can be vertically transmitted from eggs to larvae and that E. meningoseptica-mono-associated mosquitoes display significant mortality, which is further enhanced upon Plasmodium infection, suggesting a synergistic impact of E. meningoseptica and Plasmodium on mosquito survival. Conclusion The high pathogenicity and permanent association of E. meningoseptica with An. Gambiae through vertical transmission constitute attractive characteristics towards the potential design of novel mosquito/malaria biocontrol strategies. PMID:24098592

  16. Role for the Plasmodium sporozoite-specific transmembrane protein S6 in parasite motility and efficient malaria transmission.

    PubMed

    Steinbuechel, Marion; Matuschewski, Kai

    2009-02-01

    Malaria transmission occurs by intradermal deposition of Plasmodium sporozoites during the infectious bite of a female Anopheles mosquito. After formation in midgut-associated oocysts sporozoites actively enter mosquito salivary glands and subsequently invade host hepatocytes where they transform into clinically silent liver stages. To date, two sporozoite-specific transmembrane proteins have been identified that perform vital functions in natural malaria transmission. The sporozoite invasin TRAP drives sporozoite motility and target cell entry whereas the adhesin MAEBL mediates sporozoite recognition of and attachment to salivary glands. Here, we demonstrate that the sporozoite-specific transmembrane protein S6 is required for efficient malaria transmission to the vertebrate host. Targeted deletion of S6 results in severe impairment of sporozoite gliding motility and invasion of mosquito salivary glands. During sporozoite maturation S6 expression is tightly regulated by transcriptional and translational control. We propose that S6 functions together with TRAP/MIC2 family invasins to direct fast, efficient and specific cell entry and, ultimately, life cycle progression of the malaria sporozoite.

  17. Local transmission of Plasmodium vivax malaria--Palm Beach County, Florida, 2003.

    PubMed

    2003-09-26

    The majority of malaria cases diagnosed in the United States are imported, usually by persons who travel to countries where malaria is endemic. However, small outbreaks of locally acquired mosquito-transmitted malaria continue to occur. Despite certification of malaria eradication in the United States in 1970, 11 outbreaks involving 20 cases of probable locally acquired mosquito-transmitted malaria have been reported to CDC since 1992, including two reported in July 1996 from Palm Beach County, Florida (Palm Beach County Health Department, unpublished data, 1998). This report describes the investigation of seven cases of locally acquired Plasmodium vivax malaria that occurred in Palm Beach County during July-August 2003. In addition to considering malaria in the differential diagnosis for febrile patients with a history of travel to malarious areas, health-care providers also should consider malaria as a possible cause of fever among patients who have not traveled but are experiencing alternating fevers, rigors, and sweats with no obvious cause.

  18. A research agenda for malaria eradication: vaccines.

    PubMed

    2011-01-25

    Vaccines could be a crucial component of efforts to eradicate malaria. Current attempts to develop malaria vaccines are primarily focused on Plasmodium falciparum and are directed towards reducing morbidity and mortality. Continued support for these efforts is essential, but if malaria vaccines are to be used as part of a repertoire of tools for elimination or eradication of malaria, they will need to have an impact on malaria transmission. We introduce the concept of "vaccines that interrupt malaria transmission" (VIMT), which includes not only "classical" transmission-blocking vaccines that target the sexual and mosquito stages but also pre-erythrocytic and asexual stage vaccines that have an effect on transmission. VIMT may also include vaccines that target the vector to disrupt parasite development in the mosquito. Importantly, if eradication is to be achieved, malaria vaccine development efforts will need to target other malaria parasite species, especially Plasmodium vivax, where novel therapeutic vaccines against hypnozoites or preventive vaccines with effect against multiple stages could have enormous impact. A target product profile (TPP) for VIMT is proposed and a research agenda to address current knowledge gaps and develop tools necessary for design and development of VIMT is presented.

  19. Host cell deformability is linked to transmission in the human malaria parasite Plasmodium falciparum

    PubMed Central

    Aingaran, Mythili; Zhang, Rou; Law, Sue KaYee; Peng, Zhangli; Undisz, Andreas; Meyer, Evan; Diez-Silva, Monica; Burke, Thomas A.; Spielmann, Tobias; Lim, Chwee Teck; Suresh, Subra; Dao, Ming; Marti, Matthias

    2012-01-01

    SUMMARY Gametocyte maturation in Plasmodium falciparum is a critical step in the transmission of malaria. While the majority of parasites proliferate asexually in red blood cells, a small fraction of parasites undergo sexual conversion and mature over two weeks to become competent for transmission to a mosquito vector. Immature gametocytes sequester in deep tissues while mature stages must be able to circulate, pass the spleen and present themselves to the mosquito vector in order to complete transmission. Sequestration of asexual red blood cell stage parasites has been investigated in great detail. These studies have demonstrated that induction of cytoadherence properties through specific receptor-ligand interactions coincides with a significant increase in host cell stiffness. In contrast, the adherence and biophysical properties of gametocyte-infected red blood cells have not been studied systematically. Utilizing a transgenic line for 3D live imaging, in vitro capillary assays and 3D finite element whole cell modeling, we studied the role of cellular deformability in determining the circulatory characteristics of gametocytes. Our analysis shows that the red blood cell deformability of immature gametocytes displays an overall decrease followed by rapid restoration in mature gametocytes. Intriguingly, simulations suggest that along with deformability variations, the morphological changes of the parasite may play an important role in tissue distribution in vivo. Taken together we present a model, which suggests that mature but not immature gametocytes circulate in the peripheral blood for uptake in the mosquito blood meal and transmission to another human host thus ensuring long term survival of the parasite. PMID:22417683

  20. Towards eradication: three years after the tsunami of 2004, has malaria transmission been eliminated from the island of Simeulue?

    PubMed

    Sudomo, Mohammad; Arianti, Yusniar; Wahid, Isra; Safruddin, Din; Pedersen, Erling M; Charlwood, J Derek

    2010-12-01

    The island of Simeulue was the first landfall of the tsunami of December 2004. The tsunami destroyed many villages on the island, leaving one third of the population homeless. Malaria is endemic in Simeulue and an epidemic was reported to have occurred three months prior to the tsunami. Information concerning malaria was, however, not easily available. The earthquakes related to the tsunami may have created extensive potential breeding sites of Anopheles sundaicus, the probable vector, and increased vulnerability of the human population; a possibility of increased transmission made a further outbreak possible. Consequently, subsequent to the tsunami, considerable amounts of aid, including anti-malarial measures such as insecticide treated mosquito-nets, were deployed on the island. A series of island-wide cross-sectional surveys were conducted in 2005-2007 to determine whether these had had any effect on malaria prevalence. Larval sampling, and CDC light-trap and landing collections of hungry mosquitoes were also undertaken. The results indicate that despite the continuing presence of potential vectors in some places the anti-malaria measures introduced following the tsunami have controlled, and may be close to eliminating, malaria from the island.

  1. Interferon-γ responses to Plasmodium falciparum vaccine candidate antigens decrease in the absence of malaria transmission

    PubMed Central

    Ochola, Lyticia; Ngwena, Gideon A.M.; Ayodo, George; Hodges, James S.; Noland, Gregory S.; John, Chandy C.

    2017-01-01

    Background Malaria elimination campaigns are planned or active in many countries. The effects of malaria elimination on immune responses such as antigen-specific IFN- γ responses are not well characterized. Methods IFN- γ responses to the P. falciparum antigens circumsporozoite protein, liver stage antigen-1, thrombospondin-related adhesive protein, apical membrane antigen-1, MB2, and merozoite surface protein-1 were tested by ELISA in 243 individuals in highland Kenya in April 2008, October 2008, and April 2009, after a one-year period of interrupted malaria transmission from April 2007 to March 2008. Results While one individual (0.4%) tested positive for P. falciparum by PCR inOctober 2008 and another two (0.9%) tested positive in April 2009, no clinical malaria cases were detected during weekly visits. Levels of IFN-γ to all antigens decreased significantly from April 2008 to April 2009 (all P < 0.001). Discussion Naturally acquired IFN- γ responses to P. falciparum antigensare short-lived in the absence of repeated P. falciparum infection. Even short periods of malaria interruption may significantly decrease IFN-γ responses to P. falciparum antigens. PMID:28097063

  2. Modeling the effects of relapse in the transmission dynamics of malaria parasites.

    PubMed

    Aguas, Ricardo; Ferreira, Marcelo U; Gomes, M Gabriela M

    2012-01-01

    Often regarded as "benign," Plasmodium vivax infections lay in the shadows of the much more virulent P. falciparum infections. However, about 1.98 billion people are at risk of both parasites worldwide, stressing the need to understand the epidemiology of Plasmodium vivax, particularly under the scope of decreasing P. falciparum prevalence and ecological interactions between both species. Two epidemiological observations put the dynamics of both species into perspective: (1) ACT campaigns have had a greater impact on P. falciparum prevalence. (2) Complete clinical immunity is attained at younger ages for P. vivax, under similar infection rates. We systematically compared two mathematical models of transmission for both Plasmodium species. Simulations suggest that an ACT therapy combined with a hypnozoite killing drug would eliminate both species. However, P. vivax elimination is predicted to be unstable. Differences in age profiles of clinical malaria can be explained solely by P. vivax's ability to relapse, which accelerates the acquisition of clinical immunity and serves as an immunity boosting mechanism. P. vivax transmission can subsist in areas of low mosquito abundance and is robust to drug administration initiatives due to relapse, making it an inconvenient and cumbersome, yet less lethal alternative to P. falciparum.

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

    PubMed

    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 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. Ape malaria transmission and potential for ape-to-human transfers in Africa

    PubMed Central

    Makanga, Boris; Yangari, Patrick; Rahola, Nil; Rougeron, Virginie; Elguero, Eric; Boundenga, Larson; Moukodoum, Nancy Diamella; Okouga, Alain Prince; Arnathau, Céline; Durand, Patrick; Willaume, Eric; Ayala, Diego; Fontenille, Didier; Ayala, Francisco J.; Renaud, François; Ollomo, Benjamin; Prugnolle, Franck; Paupy, Christophe

    2016-01-01

    Recent studies have highlighted the large diversity of malaria parasites infecting African great apes (subgenus Laverania) and their strong host specificity. Although the existence of genetic incompatibilities preventing the cross-species transfer may explain host specificity, the existence of vectors with a high preference for a determined host represents another possibility. To test this hypothesis, we undertook a 15-mo-long longitudinal entomological survey in two forest regions of Gabon, where wild apes live, at different heights under the canopy. More than 2,400 anopheline mosquitoes belonging to 18 species were collected. Among them, only three species of Anopheles were found infected with ape Plasmodium: Anopheles vinckei, Anopheles moucheti, and Anopheles marshallii. Their role in transmission was confirmed by the detection of the parasites in their salivary glands. Among these species, An. vinckei showed significantly the highest prevalence of infection and was shown to be able to transmit parasites of both chimpanzees and gorillas. Transmission was also shown to be conditioned by seasonal factors and by the heights of capture under the canopy. Moreover, human landing catches of sylvan Anopheles demonstrated the propensity of these three vector species to feed on humans when available. Our results suggest therefore that the strong host specificity observed in the Laveranias is not linked to a specific association between the vertebrate host and the vector species and highlight the potential role of these vectors as bridge between apes and humans. PMID:27071123

  5. Improving Malaria Control in West Africa: Interruption of Transmission as a Paradigm Shift

    PubMed Central

    Doumbia, Seydou O.; Ndiaye, Daouda; Koita, Ousmane A.; Diakité, Mahamadou; Nwakanma, Davis; Coulibaly, Mamadou; Traoré, Sekou F.; Keating, Joseph; Milner, Danny A.; Ndiaye, Jean-Louis; Sene, Papa Diogoye; Ahouidi, Ambroise; Dieye, Tandakha N.; Gaye, Oumar; Okebe, Joseph; Ceesay, Serign J.; Ngwa, Alfred; Oriero, Eniyou C.; Konaté, Lassana; Sy, Ngayo; Jawara, Musa; Faye, Ousmane; Kéita, Moussa; Cissé, Moussa; Sogoba, Nafomon; Poudiougou, Belco; Diawara, Sory; Sangaré, Lansana; Coulibaly, Tinzana; Seck, Ibrahima; Abubakar, Ismaela; Gomis, Jules; Mather, Frances J.; Sissako, Aliou; Diarra, Ayouba; Kandeh, Balla; Whalen, Christopher; Moyer, Brian; Nnedu, Obinna; Thiero, Oumar; Bei, Amy K.; Daniels, Rachel; Miura, Kazutoyo; Long, Carole A.; Fairhurst, Rick M.; Duraisingh, Manoj; Muskavitch, Marc A.T.; D’Alessandro, Umberto; Conway, David J.; Volkman, Sarah K.; Valim, Clarissa; Wirth, Dyann F.; Krogstad, Donald J.

    2011-01-01

    With the paradigm shift from the reduction of morbidity and mortality to the interruption of transmission, the focus of malaria control broadens from symptomatic infections in children ≤ 5 years of age to include asymptomatic infections in older children and adults. In addition, as control efforts intensify and the number of interventions increases, there will be decreases in prevalence, incidence and transmission with additional decreases in morbidity and mortality. Expected secondary consequences of these changes include upward shifts in the peak ages for infection (parasitemia) and disease, increases in the ages for acquisition of antiparasite humoral and cellular immune responses and increases in false-negative blood smears and rapid diagnostic tests. Strategies to monitor these changes must include: 1] studies of the entire population (that are not restricted to children ≤ 5 or ≤ 10 years of age), 2] study sites in both cities and rural areas (because of increasing urbanization across sub-Saharan Africa) and 3] innovative strategies for surveillance as the prevalence of infection decreases and the frequency of false-negative smears and rapid diagnostic tests increases. PMID:22142790

  6. A review of spatial technologies with applications for malaria transmission modelling and control in Africa.

    PubMed

    Gebreslasie, Michael T

    2015-11-26

    Spatial technologies, i.e. geographic information systems, remote sensing, and global positioning systems, offer an opportunity for rapid assessment of malaria endemic areas. These technologies coupled with prevalence/incidence data can provide reliable estimates of population at risk, predict disease distributions in areas that lack baseline data and provide guidance for intervention strategies, so that scarce resources can be allocated in a cost-effective manner. This review focuses on the spatial technology applications that have been used in epidemiology and control of malaria in Africa. Peer-reviewed papers identified through a PubMed search using the following keywords: geospatial technology OR Geographic Information Systems OR Remote Sensing OR Earth Observation OR Global Positioning Systems OR geospatial modelling OR malaria incidence OR malaria prevalence OR malaria risk prediction OR malaria mapping AND malaria AND Africa were used. These included mapping malaria incidence and prevalence, assessing the relationship between malaria and environmental variables as well as applications for malaria early warning systems. The potential of new spatial technology applications utilising emerging satellite information, as they hold promise to further enhance infectious risk mapping and disease prediction, are outlined. We stress current research needs to overcome some of the remaining challenges of spatial technology applications for malaria so that further and sustainable progress can be made to control and eliminate this disease.

  7. Quantifying behavioural interactions between humans and mosquitoes: Evaluating the protective efficacy of insecticidal nets against malaria transmission in rural Tanzania

    PubMed Central

    Killeen, Gerry F; Kihonda, Japhet; Lyimo, Edith; Oketch, Fred R; Kotas, Maya E; Mathenge, Evan; Schellenberg, Joanna A; Lengeler, Christian; Smith, Thomas A; Drakeley, Chris J

    2006-01-01

    Background African malaria vectors bite predominantly indoors at night so sleeping under an Insecticide-Treated Net (ITN) can greatly reduce malaria risk. Behavioural adaptation by mosquitoes to increasing ITN coverage could allow vector mosquitoes to bite outside of peak sleeping hours and undermine efficacy of this key malaria prevention measure. Methods High coverage with largely untreated nets has been achieved in the Kilombero Valley, southern Tanzania through social marketing programmes. Direct surveys of nightly biting activity by An. gambiae Giles were conducted in the area before (1997) and after (2004) implementation of ITN promotion. A novel analytical model was applied to estimate the effective protection provided by an ITN, based on published experimental hut trials combined with questionnaire surveys of human sleeping behaviour and recorded mosquito biting patterns. Results An. gambiae was predominantly endophagic and nocturnal in both surveys: Approximately 90% and 80% of exposure occurred indoors and during peak sleeping hours, respectively. ITNs consistently conferred >70% protection against exposure to malaria transmission for users relative to non-users. Conclusion As ITN coverage increases, behavioural adaptation by mosquitoes remains a future possibility. The approach described allows comparison of mosquito biting patterns and ITN efficacy at multiple study sites and times. Initial results indicate ITNs remain highly effective and should remain a top-priority intervention. Combined with recently developed transmission models, this approach allows rapid, informative and cost-effective preliminary comparison of diverse control strategies in terms of protection against exposure before more costly and intensive clinical trials. PMID:17096840

  8. The biology of sexual development of Plasmodium: the design and implementation of transmission-blocking strategies.

    PubMed

    Sinden, Robert E; Carter, Richard; Drakeley, Chris; Leroy, Didier

    2012-03-16

    A meeting to discuss the latest developments in the biology of sexual development of Plasmodium and transmission-control was held April 5-6, 2011, in Bethesda, MD. The meeting was sponsored by the Bill & Melinda Gates Foundation and the National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIH/NIAID) in response to the challenge issued at the Malaria Forum in October 2007 that the malaria community should re-engage with the objective of global eradication. The consequent rebalancing of research priorities has brought to the forefront of the research agenda the essential need to reduce parasite transmission. A key component of any transmission reduction strategy must be methods to attack the parasite as it passes from man to the mosquito (and vice versa). Such methods must be rationally based on a secure understanding of transmission from the molecular-, cellular-, population- to the evolutionary-levels. The meeting represented a first attempt to draw together scientists with expertise in these multiple layers of understanding to discuss the scientific foundations and resources that will be required to provide secure progress toward the design and successful implementation of effective interventions.

  9. The biology of sexual development of Plasmodium: the design and implementation of transmission-blocking strategies

    PubMed Central

    2012-01-01

    A meeting to discuss the latest developments in the biology of sexual development of Plasmodium and transmission-control was held April 5-6, 2011, in Bethesda, MD. The meeting was sponsored by the Bill & Melinda Gates Foundation and the National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIH/NIAID) in response to the challenge issued at the Malaria Forum in October 2007 that the malaria community should re-engage with the objective of global eradication. The consequent rebalancing of research priorities has brought to the forefront of the research agenda the essential need to reduce parasite transmission. A key component of any transmission reduction strategy must be methods to attack the parasite as it passes from man to the mosquito (and vice versa). Such methods must be rationally based on a secure understanding of transmission from the molecular-, cellular-, population- to the evolutionary-levels. The meeting represented a first attempt to draw together scientists with expertise in these multiple layers of understanding to discuss the scientific foundations and resources that will be required to provide secure progress toward the design and successful implementation of effective interventions. PMID:22424474

  10. Malaria control in Nicaragua: social and political influences on disease transmission and control activities.

    PubMed

    Garfield, R

    1999-07-31

    Throughout Central America, a traditional malaria control strategy (depending on heavy use of organic pesticides) became less effective during the 1970s. In Nicaragua, an alternative strategy, based on frequent local epidemiological assessments and community participation, was developed in the 1980s. Despite war-related social instability, and continuing vector resistance, this approach was highly successful. By the end of the contra war, there finally existed organisational and ecological conditions that favoured improved malaria control. Yet the expected improvements did not occur. In the 1990s, Nicaragua experienced its worst recorded malaria epidemics. This situation was partly caused by the country's macroeconomic structural adjustment programme. Volunteers now take fewer slides and provide less treatment, malaria control workers are less motivated by the spirit of public service, and some malaria control stations charge for diagnosis or treatment. To "roll back malaria", in Nicaragua at least, will require the roll-back of some erroneous aspects of structural adjustment.

  11. A Research Agenda for Malaria Eradication: Vaccines

    PubMed Central

    2011-01-01

    Vaccines could be a crucial component of efforts to eradicate malaria. Current attempts to develop malaria vaccines are primarily focused on Plasmodium falciparum and are directed towards reducing morbidity and mortality. Continued support for these efforts is essential, but if malaria vaccines are to be used as part of a repertoire of tools for elimination or eradication of malaria, they will need to have an impact on malaria transmission. We introduce the concept of “vaccines that interrupt malaria transmission” (VIMT), which includes not only “classical” transmission-blocking vaccines that target the sexual and mosquito stages but also pre-erythrocytic and asexual stage vaccines that have an effect on transmission. VIMT may also include vaccines that target the vector to disrupt parasite development in the mosquito. Importantly, if eradication is to be achieved, malaria vaccine development efforts will need to target other malaria parasite species, especially Plasmodium vivax, where novel therapeutic vaccines against hypnozoites or preventive vaccines with effect against multiple stages could have enormous impact. A target product profile (TPP) for VIMT is proposed and a research agenda to address current knowledge gaps and develop tools necessary for design and development of VIMT is presented. PMID:21311586

  12. Suppression of transmission of malaria through source reduction: antianopheline measures applied in Israel, the United States, and Italy.

    PubMed

    Kitron, U; Spielman, A

    1989-01-01

    To provide a conceptual basis applicable to future antimalarial efforts, we sought to identify the sources of success in three notable campaigns that were consummated largely before DDT became available. A variety of measures directed against the aquatic stages of the anopheline vectors provided the main strategy for the antimalarial programs in Palestine/Israel, Italy, and the Tennessee River Valley of the United States. Source reduction-the modification or elimination of aquatic habitats to reduce mosquito breeding-was applied extensively and proved decisive. In all three regions, transmission of malaria was reduced to the point of extinction. Effective measures against anopheline larvae, in particular through source reduction, depend upon locally derived ecologic concepts that can be adapted to each vector species and applied continuously without limit of time. An integrated control program based on the long-term application of such measures can suppress transmission of malaria in edemic areas, as well as contain episodes of locally increased transmission of malaria.

  13. Evaluating local vegetation cover as a risk factor for malaria transmission: a new analytical approach using ImageJ

    PubMed Central

    2014-01-01

    Background In places where malaria transmission is unstable or is transmitted under hypoendemic conditions, there are periods where limited foci of cases still occur and people become infected. These residual “hot spots” are likely reservoirs of the parasite population and so are fundamental to the seasonal spread and decline of malaria. It is, therefore, important to understand the ecological conditions that permit vector mosquitoes to survive and forage in these specific areas. Features such as local waterways and vegetation, as well as local ecology, particularly nocturnal temperature, humidity, and vegetative sustainability, are important for modeling local mosquito behavior. Vegetation around a homestead likely provides refuge for outdoor resting of these insects and may be a risk factor for malaria transmission. Analysis of this vegetation can be done using satellite information and mapping programs, such as Google Earth, but manual quantification is difficult and can be tedious and subjective. A more objective method is required. Methods Vegetation cover in the environment is reasonably static, particularly in and around homesteads. In order to evaluate and enumerate such information, ImageJ, an image processing software, was used to analyse Google Earth satellite imagery. The number of plants, total amount of vegetation around a homestead and its percentage of the total area were calculated and related to homesteads where cases of malaria were recorded. Results Preliminary results were obtained from a series of field trials carried out in South East Zambia in the Choma and Namwala districts from a base at the Macha District Hospital. Conclusions This technique is objective, clear and simple to manipulate and has potential application to determine the role that vegetation proximal to houses may play in affecting mosquito behaviour, foraging and subsequent malaria incidence. PMID:24620929

  14. Ethical aspects of malaria control and research.

    PubMed

    Jamrozik, Euzebiusz; de la Fuente-Núñez, Vânia; Reis, Andreas; Ringwald, Pascal; Selgelid, Michael J

    2015-12-22

    Malaria currently causes more harm to human beings than any other parasitic disease, and disproportionally affects low-income populations. The ethical issues raised by efforts to control or eliminate malaria have received little explicit analysis, in comparison with other major diseases of poverty. While some ethical issues associated with malaria are similar to those that have been the subject of debate in the context of other infectious diseases, malaria also raises distinct ethical issues in virtue of its unique history, epidemiology, and biology. This paper provides preliminary ethical analyses of the especially salient issues of: (i) global health justice, (ii) universal access to malaria control initiatives, (iii) multidrug resistance, including artemisinin-based combination therapy (ACT) resistance, (iv) mandatory screening, (v) mass drug administration, (vi) benefits and risks of primaquine, and (vii) malaria in the context of blood donation and transfusion. Several ethical issues are also raised by past, present and future malaria research initiatives, in particular: (i) controlled infection studies, (ii) human landing catches, (iii) transmission-blocking vaccines, and (iv) genetically-modified mosquitoes. This article maps the terrain of these major ethical issues surrounding malaria control and elimination. Its objective is to motivate further research and discussion of ethical issues associated with malaria--and to assist health workers, researchers, and policy makers in pursuit of ethically sound malaria control practice and policy.

  15. Nightly biting cycles of malaria vectors in a heterogeneous transmission area of eastern Amazonian Brazil

    PubMed Central

    2013-01-01

    Background The biting cycle of anopheline mosquitoes is an important component in the transmission of malaria. Inter- and intraspecific biting patterns of anophelines have been investigated using the number of mosquitoes caught over time to compare general tendencies in host-seeking activity and cumulative catch. In this study, all-night biting catch data from 32 consecutive months of collections in three riverine villages were used to compare biting cycles of the five most abundant vector species using common statistics to quantify variability and deviations of nightly catches from a normal distribution. Methods Three communities were selected for study. All-night human landing catches of mosquitoes were made each month in the peridomestic environment of four houses (sites) for nine consecutive days from April 2003 to November 2005. Host-seeking activities of the five most abundant species that were previously captured infected with Plasmodium falciparum, Plasmodium malariae or Plasmodium vivax, were analysed and compared by measuring the amount of variation in numbers biting per unit time (co-efficient of variation, V), the degree to which the numbers of individuals per unit time were asymmetrical (skewness = g1) and the relative peakedness or flatness of the distribution (kurtosis = g2). To analyse variation in V, g1, and g2 within species and villages, we used mixed model nested ANOVAs (PROC GLM in SAS) with independent variables (sources of variation): year, month (year), night (year X month) and collection site (year X month). Results The biting cycles of the most abundant species, Anopheles darlingi, had the least pronounced biting peaks, the lowest mean V values, and typically non-significant departures from normality in g1 and g2. By contrast, the species with the most sharply defined crepuscular biting peaks, Anopheles marajoara, Anopheles nuneztovari and Anopheles triannulatus, showed high to moderate mean V values and, most commonly, significantly

  16. An experimental hut study to quantify the effect of DDT and airborne pyrethroids on entomological parameters of malaria transmission

    PubMed Central

    2014-01-01

    Background Current malaria vector control programmes rely on insecticides with rapid contact toxicity. However, spatial repellents can also be applied to reduce man-vector contact, which might ultimately impact malaria transmission. The aim of this study was to quantify effects of airborne pyrethroids from coils and DDT used an indoor residual spray (IRS) on entomological parameters that influence malaria transmission. Methods The effect of Transfluthrin and Metofluthrin coils compared to DDT on house entry, exit and indoor feeding behaviour of Anopheles gambiae sensu lato were measured in experimental huts in the field and in the semi-field. Outcomes were deterrence - reduction in house entry of mosquitoes; irritancy or excito-repellency – induced premature exit of mosquitoes; blood feeding inhibition and effect on mosquito fecundity. Results Transfluthrin coils, Metofluthrin coils and DDT reduced human vector contact through deterrence by 38%, 30% and 8%, respectively and induced half of the mosquitoes to leave huts before feeding (56%, 55% and 48%, respectively). Almost all mosquitoes inside huts with Metofluthrin and Transfluthrin coils and more than three quarters of mosquitoes in the DDT hut did not feed, almost none laid eggs and 67%, 72% and 70% of all mosquitoes collected from Transfluthrin, Metofluthrin and DDT huts, respectively had died after 24 hours. Conclusion This study highlights that airborne pyrethroids and DDT affect a range of anopheline mosquito behaviours that are important parameters in malaria transmission, namely deterrence, irritancy/excito-repellency and blood-feeding inhibition. These effects are in addition to significant toxicity and reduced mosquito fecundity that affect mosquito densities and, therefore, provide community protection against diseases for both users and non-users. Airborne insecticides and freshly applied DDT had similar effects on deterrence, irritancy and feeding inhibition. Therefore, it is suggested that

  17. Local mate competition and transmission bottlenecks: a new model for understanding malaria parasite and other sex ratios.

    PubMed

    Neal, Allison T; Taylor, Peter D

    2014-12-21

    The local mate competition model from sex ratio theory predicts female-biased sex ratios in populations that are highly subdivided during mating, and is thought to accord well with the population structure of malaria parasites. However, the selective advantage of female-biased sex ratios comes from the resulting increase in total reproductive output, an advantage the transmission biology of malaria parasite likely reduces. We develop a mathematical model to determine how bottlenecks in transmission that cause diminishing fitness returns from female production affect sex ratio evolution. We develop four variations of this model that incorporate whether or not parasite clones have the ability to detect others that occupy the same host and whether or not the number of clones affects the total mating population size. Our model indicates that transmission bottlenecks favor less female-biased sex ratios than those predicted under LMC. This effect is particularly pronounced if clones have no information about the presence of coexisting clones and the number of mating individuals per patch is fixed. The model could extend our understanding of malaria parasite sex ratios in three main ways. First, it identifies inconsistencies between the theoretical predictions and the data presented in a previous study, and proposes revised predictions that are more consistent with underlying biology of the parasite. Second, it may account for the positive association between parasite density and sex ratio observed within and between some species. Third, it predicts a relationship between mortality rates in the vector and sex ratios, which appears to be supported by the little existing data we have. While the inspiration for this model came from malaria parasites, it should apply to any system in which per capita dispersal success diminishes with increasing numbers of females in a patch.

  18. 4(1H)-Pyridone and 4(1H)-Quinolone Derivatives as Antimalarials with Erythrocytic, Exoerythrocytic, and Transmission Blocking Activities

    PubMed Central

    Monastyrskyi, Andrii; Kyle, Dennis E.; Manetsch, Roman

    2015-01-01

    Infectious diseases are the second leading cause of deaths in the world with malaria being responsible for approximately the same amount of deaths as cancer in 2012. Despite the success in malaria prevention and control measures decreasing the disease mortality rate by 45% since 2000, the development of single-dose therapeutics with radical cure potential is required to completely eradicate this deadly condition. Targeting multiple stages of the malaria parasite is becoming a primary requirement for new candidates in antimalarial drug discovery and development. Recently, 4(1H)-pyridone, 4(1H)-quinolone, 1,2,3,4-tetrahydroacridone, and phenoxyethoxy-4(1H)-quinolone chemotypes have been shown to be antimalarials with blood stage activity, liver stage activity, and transmission blocking activity. Advancements in structure-activity relationship and structure-property relationship studies, biological evaluation in vitro and in vivo, as well as pharmacokinetics of the 4(1H)-pyridone and 4(1H)-quinolone chemotypes will be discussed. PMID:25116582

  19. Response prediction techniques and case studies of a path blocking system based on Global Transmissibility Direct Transmissibility method

    NASA Astrophysics Data System (ADS)

    Wang, Zengwei; Zhu, Ping; Zhao, Jianxuan

    2017-02-01

    In this paper, the prediction capabilities of the Global Transmissibility Direct Transmissibility (GTDT) method are further developed. Two path blocking techniques solely using the easily measured variables of the original system to predict the response of a path blocking system are generalized to finite element models of continuous systems. The proposed techniques are derived theoretically in a general form for the scenarios of setting the response of a subsystem to zero and of removing the link between two directly connected subsystems. The objective of this paper is to verify the reliability of the proposed techniques by finite element simulations. Two typical cases, the structural vibration transmission case and the structure-borne sound case, in two different configurations are employed to illustrate the validity of proposed techniques. The points of attention for each case have been discussed, and conclusions are given. It is shown that for the two cases of blocking a subsystem the proposed techniques are able to predict the new response using measured variables of the original system, even though operational forces are unknown. For the structural vibration transmission case of removing a connector between two components, the proposed techniques are available only when the rotational component responses of the connector are very small. The proposed techniques offer relative path measures and provide an alternative way to deal with NVH problems. The work in this paper provides guidance and reference for the engineering application of the GTDT prediction techniques.

  20. Establishing the extent of malaria transmission and challenges facing pre-elimination in the Republic of Djibouti

    PubMed Central

    2011-01-01

    Background Countries aiming for malaria elimination require a detailed understanding of the current intensity of malaria transmission within their national borders. National household sample surveys are now being used to define infection prevalence but these are less efficient in areas of exceptionally low endemicity. Here we present the results of a national malaria indicator survey in the Republic of Djibouti, the first in sub-Saharan Africa to combine parasitological and serological markers of malaria, to evaluate the extent of transmission in the country and explore the potential for elimination. Methods A national cross-sectional household survey was undertaken from December 2008 to January 2009. A finger prick blood sample was taken from randomly selected participants of all ages to examine for parasitaemia using rapid diagnostic tests (RDTs) and confirmed using Polymerase Chain Reaction (PCR). Blood spots were also collected on filter paper and subsequently used to evaluate the presence of serological markers (combined AMA-1 and MSP-119) of Plasmodium falciparum exposure. Multivariate regression analysis was used to determine the risk factors for P. falciparum infection and/or exposure. The Getis-Ord G-statistic was used to assess spatial heterogeneity of combined infections and serological markers. Results A total of 7151 individuals were tested using RDTs of which only 42 (0.5%) were positive for P. falciparum infections and confirmed by PCR. Filter paper blood spots were collected for 5605 individuals. Of these 4769 showed concordant optical density results and were retained in subsequent analysis. Overall P. falciparum sero-prevalence was 9.9% (517/4769) for all ages; 6.9% (46/649) in children under the age of five years; and 14.2% (76/510) in the oldest age group (≥ 50 years). The combined infection and/or antibody prevalence was 10.5% (550/4769) and varied from 8.1% to 14.1% but overall regional differences were not statistically significant (χ2

  1. The role of spatial mobility in malaria transmission in the Brazilian Amazon: The case of Porto Velho municipality, Rondônia, Brazil (2010-2012)

    PubMed Central

    Sabroza, Paulo Chagastelles; de Carvalho, Lino Augusto Sander; Nobre, Carlos Afonso

    2017-01-01

    Background This study aims to describe the role of mobility in malaria transmission by discussing recent changes in population movements in the Brazilian Amazon and developing a flow map of disease transmission in this region. Methodology/Principal findings This study presents a descriptive analysis using an ecological approach on regional and local scales. The study location was the municipality of Porto Velho, which is the capital of Rondônia state, Brazil. Our dataset was obtained from the official health database, the population census and an environmental database. During 2000–2007 and 2007–2010, the Porto Velho municipality had an annual population growth of 1.42% and 5.07%, respectively. This population growth can be attributed to migration, which was driven by the construction of the Madeira River hydroelectric complex. From 2010 to 2012, 63,899 malaria-positive slides were reported for residents of Porto Velho municipality; 92% of the identified samples were autochthonous, and 8% were allochthonous. The flow map of patients' movements between residential areas and areas of suspected infection showed two patterns of malaria transmission: 1) commuting between residential areas and the Jirau hydropower dam reservoir, and 2) movements between urban areas and farms and resorts in rural areas. It was also observed that areas with greater occurrences of malaria were characterized by a low rate of deforestation. Conclusions The Porto Velho municipality exhibits high malaria endemicity and plays an important role in disseminating the parasite to other municipalities in the Amazon and even to non-endemic areas of the country. Migration remains an important factor for the occurrence of malaria. However, due to recent changes in human occupation of the Brazilian Amazon, characterized by intense expansion of transportation networks, commuting has also become an important factor in malaria transmission. The magnitude of this change necessitates a new model to

  2. Transmission-Blocking Vaccines: Focus on Anti-Vector Vaccines against Tick-Borne Diseases.

    PubMed

    Neelakanta, Girish; Sultana, Hameeda

    2015-06-01

    Tick-borne diseases are a potential threat that account for significant morbidity and mortality in human population worldwide. Vaccines are not available to treat several of the tick-borne diseases. With the emergence and resurgence of several tick-borne diseases, emphasis on the development of transmission-blocking vaccines remains increasing. In this review, we provide a snap shot on some of the potential candidates for the development of anti-vector vaccines (a form of transmission-blocking vaccines) against wide range of hard and soft ticks that include Ixodes, Haemaphysalis, Dermacentor, Amblyomma, Rhipicephalus and Ornithodoros species.

  3. Biology, distribution and control of Anopheles (Cellia) minimus in the context of malaria transmission in northeastern India.

    PubMed

    Dev, Vas; Manguin, Sylvie

    2016-11-15

    Among six dominant mosquito vector species involved in malaria transmission in India, Anopheles minimus is a major species in northeast India and held responsible for focal disease outbreaks characterized by high-rise of Plasmodium falciparum infections and attributable death cases. It has been now genetically characterized that among the three-member species of the Minimus Complex spread in Asia, An. minimus (former species A) is prevalent in India including northeastern states and east-central state of Odisha. It is recorded in all seasons and accounts for perennial transmission evidenced by records of sporozoite infections. This species is highly anthropophilic, and largely endophilic and endophagic, recorded breeding throughout the year in slow flowing seepage water streams. The populations of An. minimus in India are reported to be highly diverse indicating population expansion with obvious implications for judicious application of vector control interventions. Given the rapid ecological changes due to deforestation, population migration and expansion and developmental activities, there is scope for further research on the existence of potential additional sibling species within the An. minimus complex and bionomics studies on a large geographical scale for species sanitation. For control of vector populations, DDT continues to be applied on account of retaining susceptibility status even after decades of residual spraying. Anopheles minimus is a highly adaptive species and requires continuous and sustained efforts for its effective control to check transmission and spread of drug-resistant malaria. Anopheles minimus populations are reportedly diminishing in northeastern India whereas it has staged comeback in east-central State of Odisha after decades of disappearance with its eco-biological characteristics intact. It is the high time to siege the opportunity for strengthening interventions against this species for its population diminution to sub

  4. The Dynamics of Transmission and Spatial Distribution of Malaria in Riverside Areas of Porto Velho, Rondônia, in the Amazon Region of Brazil

    PubMed Central

    Katsuragawa, Tony Hiroshi; Gil, Luiz Herman Soares; Tada, Mauro Shugiro; de Almeida e Silva, Alexandre; Costa, Joana D'Arc Neves; da Silva Araújo, Maisa; Escobar, Ana Lúcia; Pereira da Silva, Luiz Hildebrando

    2010-01-01

    The study area in Rondônia was the site of extensive malaria epidemic outbreaks in the 19th and 20th centuries related to environmental impacts, with large immigration flows. The present work analyzes the transmission dynamics of malaria in these areas to propose measures for avoiding epidemic outbreaks due to the construction of two Hydroelectric Power Plants. A population based baseline demographic census and a malaria prevalence follow up were performed in two river side localities in the suburbs of Porto Velho city and in its rural vicinity. The quantification and nature of malaria parasites in clinical patients and asymptomatic parasite carriers were performed using microscopic and Real Time PCR methodologies. Anopheles densities and their seasonal variation were done by monthly captures for defining HBR (hourly biting rate) values. Main results: (i) malaria among residents show the riverside profile, with population at risk represented by children and young adults; (ii) asymptomatic vivax and falciparum malaria parasite carriers correspond to around 15% of adults living in the area; (iii) vivax malaria relapses were responsible for 30% of clinical cases; (iv) malaria risk for the residents was evaluated as 20–25% for vivax and 5–7% for falciparum malaria; (v) anopheline densities shown outdoors HBR values 5 to 10 fold higher than indoors and reach 10.000 bites/person/year; (vi) very high incidence observed in one of the surveyed localities was explained by a micro epidemic outbreak affecting visitors and temporary residents. Temporary residents living in tents or shacks are accessible to outdoors transmission. Seasonal fishermen were the main group at risk in the study and were responsible for a 2.6 fold increase in the malaria incidence in the locality. This situation illustrates the danger of extensive epidemic outbreaks when thousands of workers and secondary immigrant population will arrive attracted by opportunities opened by the Hydroelectric Power

  5. Long-run relative importance of temperature as the main driver to malaria transmission in Limpopo Province, South Africa: a simple econometric approach.

    PubMed

    Komen, Kibii; Olwoch, Jane; Rautenbach, Hannes; Botai, Joel; Adebayo, Adetunji

    2015-03-01

    Malaria in Limpopo Province of South Africa is shifting and now observed in originally non-malaria districts, and it is unclear whether climate change drives this shift. This study examines the distribution of malaria at district level in the province, determines direction and strength of the linear relationship and causality between malaria with the meteorological variables (rainfall and temperature) and ascertains their short- and long-run variations. Spatio-temporal method, Correlation analysis and econometric methods are applied. Time series monthly meteorological data (1998-2007) were obtained from South Africa Weather Services, while clinical malaria data came from Malaria Control Centre in Tzaneen (Limpopo Province) and South African Department of Health. We find that malaria changes and pressures vary in different districts with a strong positive correlation between temperature with malaria, r = 0.5212, and a weak positive relationship for rainfall, r = 0.2810. Strong unidirectional causality runs from rainfall and temperature to malaria cases (and not vice versa): F (1, 117) = 3.89, ρ = 0.0232 and F (1, 117) = 20.08, P < 0.001 and between rainfall and temperature, a bi-directional causality exists: F (1, 117) = 19.80; F (1,117) = 17.14, P < 0.001, respectively, meaning that rainfall affects temperature and vice versa. Results show evidence of strong existence of a long-run relationship between climate variables and malaria, with temperature maintaining very high level of significance than rainfall. Temperature, therefore, is more important in influencing malaria transmission in Limpopo Province.

  6. The conditions of malaria transmission in Katsina Province, Northern Nigeria, and a discussion of the effects of dichlorvos application*

    PubMed Central

    Foll, C. V.; Pant, C. P.

    1966-01-01

    A study has been made of the conditions of malaria transmission in the northern part of the Guinea savannah belt of West Central Africa. It was found that, in this holoendemic area, transmission occurs principally from August to December but continues on a much reduced scale throughout the rest of the year, even when anopheline densities are as low as 0.02 per hut. Longitudinal parasitological studies on infants, carried out on an area rather than an individual village basis, provide the most useful epidemiological technique during the minor transmission period. Examination of the spleens of children from areas that had been treated with dichlorvos suggested that the reduced hut anopheline densities resulting from the treatment were subsequently reflected in the reduced number of children showing markedly enlarged spleens. PMID:20604208

  7. Spatial distribution, blood feeding pattern, and role of Anopheles funestus complex in malaria transmission in central Kenya.

    PubMed

    Muturi, Ephantus J; Kamau, Luna; Jacob, Benjamin G; Muriu, Simon; Mbogo, Charles M; Shililu, Josephat; Githure, John; Novak, Robert J

    2009-10-01

    Studies were conducted to determine the role of sibling species of Anopheles funestus complex in malaria transmission in three agro-ecosystems in central Kenya. Mosquitoes were sampled indoors and outdoors, and rDNA PCR was successfully used to identify 340 specimens. Anopheles parensis (91.8%), A. funestus (6.8%), and Anopheles leesoni (1.5%) were the three sibling species identified. A. parensis was the dominant species at all study sites, while 22 of 23 A. funestus were collected in the non-irrigated study site. None of the 362 specimens tested was positive for Plasmodium falciparum circumsporozoite proteins by enzyme-linked immunosorbent assay. The most common blood-meal sources (mixed blood meals included) for A. parensis were goat (54.0%), human (47.6%), and bovine (39.7%), while the few A. funestus s.s. samples had fed mostly on humans. The human blood index (HBI) for A. parensis (mixed blood meals included) in the non-irrigated agro-ecosystem was 0.93 and significantly higher than 0.33 in planned rice agro-ecosystem. The few samples of A. funestus s.s. and A. funestus s.l. also showed a trend of higher HBI in the non-irrigated agro-ecosystem. We conclude that agricultural practices have significant influence on distribution and blood feeding behavior of A. funestus complex. Although none of the species was implicated with malaria transmission, these results may partly explain why non-irrigated agro-ecosystems are associated with higher risk of malaria transmission by this species compared to irrigated agro-ecosystems.

  8. Local prevalence and transmission of avian malaria in the Alakai Plateau of Kauai, Hawaii, U.S.A.

    PubMed

    Glad, Anouk; Crampton, Lisa H

    2015-12-01

    Avian malaria is among the most important threats to native Hawaiian forest birds. It is caused by the parasite Plasmodium relictum and is transmitted by the introduced mosquito vector Culex quinquefasciatus. Temperature increases and precipitation declines due to climate change over the last decade may be responsible for the observed recent expansion in the range and prevalence of avian malaria on the Alakai Plateau, Kauai Island. To examine the hypothesis that conditions are now favorable for transmission of malaria on the Plateau, mosquitoes were sampled with CO2 and Reiter oviposition traps at three sites (Kawaikoi, Halepa'akai, and Koke'e) on several occasions between October, 2013 and April, 2014. P. relictum infection was assessed by PCR or dissection under a microscope. We also surveyed mosquito larvae along Halepa'akai and Kawaikoi streams. We observed that Cx. quinquefasciatus is well established on the Alakai Plateau, as mosquitoes were caught on all field trips, except in April at Halepa'akai, and larvae were found throughout the year. We observed differences in adult abundance among sites and microhabitats (stream vs ridge lines).

  9. Peer-to-peer transmission of remote sensing image data using image subset block

    NASA Astrophysics Data System (ADS)

    Zhang, Feng; Hou, Zhitong; Du, Zhenhong; Liu, Renyi; Yan, Yiming

    2015-09-01

    The unprecedented amount and multiple applications of remote sensing image data have created a strong need for efficient data transmission. Commonly used in the transmission of various types of data, peer-to-peer (P2P) opens up new possibilities for the transmission of remote sensing image data. A considerable amount of work has been done toward the transmission of remote sensing data by using map tiles for fast online browsing. However, issues concerning the transmission of original image data require more volume and flexibility, which is indispensable in the application of remote sensing images. According to the spatial and band characteristics of remote sensing images, an approach using image subset blocks (ISBs) is proposed for P2P transmission of remote sensing image data. The method improves efficiency in two ways: transmitting ISBs on demand to reduce unnecessary transmission and using a P2P method to break the bandwidth bottleneck of the central server. The results of the performance evaluation reveal that compared with the traditional transmission method that uses the central server, the proposed method considerably enhances the efficiency to approach the level of general P2P file transmission.

  10. Magnitude of Malaria and Factors among Febrile Cases in Low Transmission Areas of Hadiya Zone, Ethiopia: A Facility Based Cross Sectional Study

    PubMed Central

    Gone, Terefe Fuge; Leta, Taye Janfa

    2016-01-01

    Background Despite a remarkable decline in morbidity and mortality since the era of malaria roll back strategy, it still poses a huge challenge in Ethiopia in general and in Hadiya Zone in particular. Although, there are data from routine health management information on few indicators, there is scarcity of data showing magnitude of malaria and associated factors including knowledge and practice in the study area. Therefore, the aim of this study was to assess magnitude and factors affecting malaria in low transmission areas among febrile cases attending public health facilities in Hadiya Zone, Ethiopia. Methods A facility based cross-sectional study was conducted in Hadiya Zone from May 15 to June 15, 2014. Simple random sampling was used to select the health facility while systematic random sampling technique was used to reach febrile patients attending public health facilities. Data were collected by a pre-tested structured questionnaire containing sections of socio demographic risk factors and knowledge and prevention practices of malaria. Data were entered to Epi-Info software version 3.5.4 and exported to SPSS version 16 for descriptive and logistic regression analysis. Results One hundred six (25.8%) of participating febrile patients attending at sampled health facilities were found to have malaria by microscopy. Of which, P.vivax, P.falciparum and mixed infection accounted for 76(71. 7%), 27 (25.5%) and 3 (2.8%), respectively. History of travel to malaria endemic area, [AOR: 2.59, 95% CI: (1.24, 5.38)], not using bed net, [AOR: 4.67, 95%CI:, (2.11, 10.37)], poor practice related to malaria prevention and control, [AOR: 2.28, (95%CI: (1.10, 4.74)], poor knowledge about malaria, [AOR: 5.09,95%CI: (2.26,11.50)] and estimated distance of stagnant water near to the residence, [AOR: 3.32, (95%CI: (1.13, 9.76)] were significantly associated factors of malaria positivity in the study. Conclusion The present study revealed that malaria is still a major source of

  11. Remote sensing of anophelines in rice-cropping villages in Mali: Patterns of vector abundance and malaria transmission

    NASA Astrophysics Data System (ADS)

    Diuk Wasser, Maria Ana

    The explosive population growth and widespread urbanization in Africa requires a significant increase in food production. Crop irrigation is therefore expected to increase in the future, although it is often blamed for aggravating the health risk of local communities---by providing habitats suitable for mosquitoes vectors of malaria (Anopheles gambiae s.l. and An. funestus in our study area) and other diseases. An epidemiological paradox sometimes occurs, however, when an increase in vector numbers is accompanied by a reduction of the risk of infection, due to a reduction in mosquito longevity and of their tendency to bite human (vs. animals). The objective of this dissertation was to determine how agricultural patterns mapped using satellite data affected vector densities and malaria transmission parameters in 18 rice-cropping villages in Mali. I used a combination of optical (Landsat ETM+) and synthetic aperture radar (ERS-2 SAR). Using Landsat data, rice was distinguished from other land uses with 98% accuracy and rice cohorts were discriminated with 84% accuracy (three classes) or 94% (two classes). ERS-2 SAR backscatter was correlated with the height and biomass of rice plants and was therefore useful to distinguish among rice growth stages. As in previous studies, the early vegetative stage was associated with higher larval production. SAR was further able to distinguish between agronomic practices linked to high and low-production within those early stages. The landcover maps were integrated with archived data on adult and larval anopheline densities and malaria transmission parameters. The area of several landcovers explained up to 89% of the variability in mosquito numbers. The maximum correlation was obtained when landcover was measured in a 1-km buffer area. Vector density was negatively associated to parity and anthropophilic rates. An. gambiae showed higher vectorial capacity (VC) than An. funestus , with seasonal variations. Peak VC for both species

  12. Impact of operational effectiveness of long-lasting insecticidal nets (LLINs) on malaria transmission in pyrethroid-resistant areas

    PubMed Central

    2013-01-01

    Background A dynamic study on the transmission of malaria was conducted in two areas (R+ area: Low resistance area; R+++ area: High resistance area) in the department of Plateau in South Eastern Benin, where the population is protected by Long Lasting Insecticidal Nets (LLINs). The aim of this study was to determine if the resistance of malaria vectors to insecticides has an impact on their behavior and on the effectiveness of LLINs in the reduction of malaria transmission. Methods Populations of Anopheles gambiae s.l. were sampled monthly by human landing catch in the two areas to evaluate human biting rates (HBR). Collected mosquitoes were identified morphologically and female Anopheles mosquitoes were tested for the presence of Plasmodium falciparum antigen as assessed using ELISA. The entomological inoculation rate (EIR) was also calculated (EIR = HBR x sporozoitic index [S]). We estimated the parity rate by dissecting the females of An. gambiae. Finally, window catch and spray catch were conducted in order to assess the blood feeding rate and the exophily rate of vectors. Results After 6 months of tracking the mosquito's behavior in contact with the LLINs (Olyset) in R+++ and R+ areas, the entomological indicators of the transmission of malaria (parity rate and sporozoitic index) were similar in the two areas. Also, An. gambiae populations showed the same susceptibility to P. falciparum in both R+ and R+++ areas. The EIR and the exophily rate are higher in R+ area than in R+++ area. But the blood-feeding rate is lower in R+ area comparing to R+++. Conclusion The highest entomological inoculation rate observed in R+ area is mostly due to the strong aggressive density of An. gambiae recorded in one of the study localities. On the other hand, the highest exophily rate and the low blood-feeding rate recorded in R+ area compared to R+++ area are not due to the resistance status of An. gambiae, but due to the differences in distribution and availability of

  13. Potential threat of malaria epidemics in a low transmission area, as exemplified by São Tomé and Príncipe

    PubMed Central

    2010-01-01

    Background Plasmodium falciparum is the major cause of malaria infection in the island of São Tomé, in the Republic of São Tomé and Príncipe (STP), with an incidence of 40 - 50% before 2004. Since 2004, through the coordination of the Ministry of Health of STP and their Centro Nacional de Endemias (CNE), an integrated malaria control programme has been intensively deployed on the island of São Tomé. Malaria morbidity and mortality decreased by 95% after three years of effective intervention. In the low transmission settings, however, malaria seasonal fluctuation can be a potential problem directly related to epidemics if ongoing control measures are interrupted. Studies on a number of associated factors with malaria epidemics and the measures taken to respond to outbreaks are presented. Methods The integrated malaria control programme included indoor residual spraying (IRS), long-lasting insecticidal nets (LLINs), intermittent preventive therapy for pregnant women, as well as early diagnosis and prompt treatment with artemisinin-based combination therapy (ACT). Regular implementation of an island-wide IRS programme was carried out yearly in 2004-2007, and enhanced throughout the island in 2009. Malaria incidence and prevalence were estimated based on passive case detection and mass screening, respectively. Slide positivity rates were used for monitoring the beginning of a malaria epidemic or a seasonal peak. Results A steep decline of ca. 95% of malaria morbidity and mortality was observed between 2004 and 2008 with use of the combined control methods. Malaria incidence was 2.0%, 1.5%, and 3.0% for 2007, 2008, and 2009, respectively. In April 2008, a cross-sectional country-wide surveillance showed malaria prevalence of 3.5%, of which 95% cases were asymptomatic carriers. Only 50% of asymptomatic carriers were cured with ACT treatment, while 90% of the symptomatic patients were cured by ACT treatment as confirmed with a follow up study. Malaria morbidity

  14. Geographic coincidence of increased malaria transmission hazard and vulnerability occurring at the periphery of two Tanzanian villages

    PubMed Central

    2013-01-01

    Background The goal of malaria elimination necessitates an improved understanding of any fine-scale geographic variations in transmission risk so that complementary vector control tools can be integrated into current vector control programmes as supplementary measures that are spatially targeted to maximize impact upon residual transmission. This study examines the distribution of host-seeking malaria vectors at households within two villages in rural Tanzania. Methods Host-seeking mosquitoes were sampled from 72 randomly selected households in two villages on a monthly basis throughout 2008 using CDC light-traps placed beside occupied nets. Spatial autocorrelation in the dataset was examined using the Moran’s I statistic and the location of any clusters was identified using the Getis-Ord Gi* statistic. Statistical associations between the household characteristics and clusters of mosquitoes were assessed using a generalized linear model for each species. Results For both Anopheles gambiae sensu lato and Anopheles funestus, the density of host-seeking females was spatially autocorrelated, or clustered. For both species, houses with low densities were clustered in the semi-urban village centre while houses with high densities were clustered in the periphery of the villages. Clusters of houses with low or high densities of An. gambiae s.l. were influenced by the number of residents in nearby houses. The occurrence of high-density clusters of An. gambiae s.l. was associated with lower elevations while An. funestus was also associated with higher elevations. Distance from the village centre was also positively correlated with the number of household occupants and having houses constructed with open eaves. Conclusion The results of the current study highlight that complementary vector control tools could be most effectively targeted to the periphery of villages where the households potentially have a higher hazard (mosquito densities) and vulnerability (open eaves and

  15. The use of insecticide-treated nets for reducing malaria morbidity among children aged 6-59 months, in an area of high malaria transmission in central Côte d'Ivoire

    PubMed Central

    2010-01-01

    Background Long-lasting insecticidal nets (LLINs) are an important tool for controlling malaria. Much attention has been devoted to determine both the effect of LLINs on the reduction of Plasmodium infection rate and on clinically-confirmed malaria cases in sub-Saharan Africa. We carried out an epidemiological study to investigate whether LLINs impact on Plasmodium prevalence rate and the proportion of clinically-confirmed malaria cases, in five villages in the district of Toumodi, central Côte d'Ivoire. Methods From April 2007 to November 2008, a community-based malaria control programme was implemented in the study villages, which involved large-scale distribution of LLINs, and training and sensitization activities within the community. We determined the effect of this programme on Plasmodium prevalence rate, clinically-confirmed malaria cases and proportion of high parasitaemia rates in children aged 6-59 months through a series of cross-sectional surveys starting in April 2007 and repeated once every 6 months. Results We observed a significant decrease in the mean P. falciparum prevalence rate from April 2007 to April 2008 (p = 0.029). An opposite trend was observed from November 2007 to November 2008 when P. falciparum prevalence rate increased significantly (p = 0.003). Highly significant decreases in the proportions of clinical malaria cases were observed between April 2007 and April 2008 (p < 0.001), and between November 2007 and November 2008 (p = 0.001). Conclusions Large-scale distribution of LLINs, accompanied by training and sensitization activities, significantly reduced Plasmodium prevalence rates among young children in the first year of the project, whereas overall clinical malaria rates dropped over the entire 18-month project period. A decrease in community motivation to sleep under bed nets, perhaps along with changing patterns of malaria transmission, might explain the observed increase in the Plasmodium prevalence rate between November 2007

  16. Field Evaluation of a Push-Pull System to Reduce Malaria Transmission

    PubMed Central

    Menger, David J.; Omusula, Philemon; Holdinga, Maarten; Homan, Tobias; Carreira, Ana S.; Vandendaele, Patrice; Derycke, Jean-Luc; Mweresa, Collins K.; Mukabana, Wolfgang Richard; van Loon, Joop J. A.; Takken, Willem

    2015-01-01

    Malaria continues to place a disease burden on millions of people throughout the tropics, especially in sub-Saharan Africa. Although efforts to control mosquito populations and reduce human-vector contact, such as long-lasting insecticidal nets and indoor residual spraying, have led to significant decreases in malaria incidence, further progress is now threatened by the widespread development of physiological and behavioural insecticide-resistance as well as changes in the composition of vector populations. A mosquito-directed push-pull system based on the simultaneous use of attractive and repellent volatiles offers a complementary tool to existing vector-control methods. In this study, the combination of a trap baited with a five-compound attractant and a strip of net-fabric impregnated with micro-encapsulated repellent and placed in the eaves of houses, was tested in a malaria-endemic village in western Kenya. Using the repellent delta-undecalactone, mosquito house entry was reduced by more than 50%, while the traps caught high numbers of outdoor flying mosquitoes. Model simulations predict that, assuming area-wide coverage, the addition of such a push-pull system to existing prevention efforts will result in up to 20-fold reductions in the entomological inoculation rate. Reductions of such magnitude are also predicted when mosquitoes exhibit a high resistance against insecticides. We conclude that a push-pull system based on non-toxic volatiles provides an important addition to existing strategies for malaria prevention. PMID:25923114

  17. The role of vector control in stopping the transmission of malaria: threats and opportunities.

    PubMed

    Hemingway, Janet

    2014-01-01

    Malaria control, and that of other insect borne diseases such as dengue, is heavily dependent on our ability to control the mosquito populations that transmit these diseases. The major push over the last decade to reduce the global burden of malaria has been driven by the distribution of pyrethroid insecticide-treated bednets and an increase in coverage of indoor residual spraying (IRS). This has reduced malaria deaths by a third. Progress towards the goal of reducing this further is threatened by lack of funding and the selection of drug and insecticide resistance. When malaria control was initially scaled up, there was little pyrethroid resistance in the major vectors, today there is no country in Africa where the vectors remain fully susceptible to pyrethroids. The first pyrethroid resistance mechanisms to be selected produced low-level resistance which had little or no operational significance. More recently, metabolically based resistance has been selected, primarily in West Africa, which in some mosquito populations produces more than 1000-fold resistance. As this spreads the effectiveness of pyrethroid-based bednets and IRS will be compromised. New public health insecticides are not readily available. The pipeline of agrochemical insecticides that can be re-purposed for public health dried up 30 years ago when the target product profile for agricultural insecticides shifted from broad spectrum, stable, contact-acting insecticides to narrow spectrum stomach poisons that could be delivered through the plant. A public-private partnership, the Innovative Vector Control Consortium, was established in 2005 to stimulate the development of new public health pesticides. Nine potential new classes of chemistry are in the pipeline, with the intention of developing three into new insecticides. While this has been successfully achieved, it will still take 6-9 years for new insecticides to reach the market. Careful management of the resistance situation in the interim

  18. 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

    PubMed Central

    Gimnig, John E.; Otieno, Peter; Were, Vincent; Marwanga, Doris; Abong’o, Daisy; Wiegand, Ryan; Williamson, John; Wolkon, Adam; Zhou, Ying; Bayoh, M. Nabie; Lobo, Neil F.; Laserson, Kayla; Kariuki, Simon; Hamel, Mary J.

    2016-01-01

    Background 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). Methods 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. Results 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

  19. Combined DNA extraction and antibody elution from filter papers for the assessment of malaria transmission intensity in epidemiological studies

    PubMed Central

    2013-01-01

    Background Informing and evaluating malaria control efforts relies on knowledge of local transmission dynamics. Serological and molecular tools have demonstrated great sensitivity to quantify transmission intensity in low endemic settings where the sensitivity of traditional methods is limited. Filter paper blood spots are commonly used a source of both DNA and antibodies. To enhance the operational practicability of malaria surveys, a method is presented for combined DNA extraction and antibody elution. Methods Filter paper blood spots were collected as part of a large cross-sectional survey in the Kenyan highlands. DNA was extracted using a saponin/chelex method. The eluate of the first wash during the DNA extraction process was used for antibody detection and compared with previously validated antibody elution procedures. Antibody elution efficiency was assessed by total IgG ELISA for malaria antigens apical membrane antigen-1 (AMA-1) and merozoite-surface protein-1 (MSP-142). The sensitivity of nested 18S rRNA and cytochrome b PCR assays and the impact of doubling filter paper material for PCR sensitivity were determined. The distribution of cell material and antibodies throughout filter paper blood spots were examined using luminescent and fluorescent reporter assays. Results Antibody levels measured after the combined antibody/DNA extraction technique were strongly correlated to those measured after standard antibody elution (p < 0.0001). Antibody levels for both AMA-1 and MSP-142 were generally slightly lower (11.3-21.4%) but age-seroprevalence patterns were indistinguishable. The proportion of parasite positive samples ranged from 12.9% to 19.2% in the different PCR assays. Despite strong agreement between outcomes of different PCR assays, none of the assays detected all parasite-positive individuals. For all assays doubling filter paper material for DNA extraction increased sensitivity. The concentration of cell and antibody material was not

  20. Pooled Amplicon Deep Sequencing of Candidate Plasmodium falciparum Transmission-Blocking Vaccine Antigens

    PubMed Central

    Juliano, Jonathan J.; Parobek, Christian M.; Brazeau, Nicholas F.; Ngasala, Billy; Randrianarivelojosia, Milijaona; Lon, Chanthap; Mwandagalirwa, Kashamuka; Tshefu, Antoinette; Dhar, Ravi; Das, Bidyut K.; Hoffman, Irving; Martinson, Francis; Mårtensson, Andreas; Saunders, David L.; Kumar, Nirbhay; Meshnick, Steven R.

    2016-01-01

    Polymorphisms within Plasmodium falciparum vaccine candidate antigens have the potential to compromise vaccine efficacy. Understanding the allele frequencies of polymorphisms in critical binding regions of antigens can help in the designing of strain-transcendent vaccines. Here, we adopt a pooled deep-sequencing approach, originally designed to study P. falciparum drug resistance mutations, to study the diversity of two leading transmission-blocking vaccine candidates, Pfs25 and Pfs48/45. We sequenced 329 P. falciparum field isolates from six different geographic regions. Pfs25 showed little diversity, with only one known polymorphism identified in the region associated with binding of transmission-blocking antibodies among our isolates. However, we identified four new mutations among eight non-synonymous mutations within the presumed antibody-binding region of Pfs48/45. Pooled deep sequencing provides a scalable and cost-effective approach for the targeted study of allele frequencies of P. falciparum candidate vaccine antigens. PMID:26503281

  1. Cost-Effectiveness Analysis of Test-Based versus Presumptive Treatment of Uncomplicated Malaria in Children under Five Years in an Area of High Transmission in Central Ghana

    PubMed Central

    Tawiah, Theresa; Hansen, Kristian Schultz; Baiden, Frank; Bruce, Jane; Tivura, Mathilda; Delimini, Rupert; Amengo-Etego, Seeba; Chandramohan, Daniel; Owusu-Agyei, Seth; Webster, Jayne

    2016-01-01

    Background The presumptive approach of confirming malaria in health facilities leads to over-diagnosis of malaria, over use of anti-malaria drugs and the risk of drug resistance development. WHO recommends parasitological confirmation before treatment with artemisinin-based combination therapy (ACT) in all suspected malaria patients. The use of malaria rapid diagnostic tests (mRDTs) would make it possible for prescribers to diagnose malaria at point-of-care and better target the use of antimalarials. Therefore, a cost-effectiveness analysis was performed on the introduction of mRDTs for management of malaria in under-five children in a high transmission area in Ghana where presumptive diagnosis was the norm in public health centres. Methods A cluster-randomised controlled trial where thirty-two health centres were randomised into test-based diagnosis of malaria using mRDTs (intervention) or clinical judgement (control) was used to measure the effect of mRDTs on appropriate treatment: ‘a child with a positive reference diagnosis prescribed a course of ACT or a child with a negative reference diagnosis not given an ACT’. Cost data was collected from five purposively selected health centres and used to estimate the health sector costs of performing an mRDT and treat children for malaria and other common febrile illnesses. Costs of training healthcare personnel and supervision in the study period were also collected. A sample of caregivers to children participating in the trial was interviewed about household cost incurred on transport, drugs, fees, and special food during a period of one week after the health centre visit as well as days unable to work. A decision model approach was used to calculate the incremental cost-effectiveness ratios (ICERs). Univariate and multivariate sensitivity analyses were applied to assess the robustness of ICERs. Results The availability of mRDTs for malaria diagnosis resulted in fewer ACT treatments compared to the clinical

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

    PubMed Central

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

    2016-01-01

    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. PMID:27121004

  3. Giant-enhancement of extraordinary optical transmission through nanohole arrays blocked by plasmonic gold mushroom caps

    NASA Astrophysics Data System (ADS)

    Zhang, Qing; Hu, Pidong; Liu, Chengpu

    2015-01-01

    An improved plasmonic hole array nanostructure model with the holes blocked by gold mushroom caps is proposed and it can realize a giant transmission with efficiency up to 65%, 182% larger than the unblocked nanohole array, due to the strong coupling between caps and holes, which plays the role of a cavity antenna. Moreover, the numerical investigation confirms that it provides more consistency with the practical experimental situations, than the nanodisk model instead. As expected, the light transmission sensitively depends on the geometric parameters of this new nanostructure; as the cap-hole's gap or cap's diameter vary, there always exists an optimal transmission efficiency. More interesting is that the corresponding optimal wavelength decreases with the gap's increment or the diameter's decrement, particularly in an exponential decaying way, and the decay rate is obviously influenced by the cap's parameters.

  4. The Impact of Hotspot-Targeted Interventions on Malaria Transmission in Rachuonyo South District in the Western Kenyan Highlands: A Cluster-Randomized Controlled Trial

    PubMed Central

    Bradley, John; Knight, Philip; Stone, William; Osoti, Victor; Makori, Euniah; Owaga, Chrispin; Odongo, Wycliffe; China, Pauline; Shagari, Shehu; Doumbo, Ogobara K.; Sauerwein, Robert W.; Kariuki, Simon; Drakeley, Chris; Stevenson, Jennifer; Cox, Jonathan

    2016-01-01

    Background Malaria transmission is highly heterogeneous, generating malaria hotspots that can fuel malaria transmission across a wider area. Targeting hotspots may represent an efficacious strategy for reducing malaria transmission. We determined the impact of interventions targeted to serologically defined malaria hotspots on malaria transmission both inside hotspots and in surrounding communities. Methods and Findings Twenty-seven serologically defined malaria hotspots were detected in a survey conducted from 24 June to 31 July 2011 that included 17,503 individuals from 3,213 compounds in a 100-km2 area in Rachuonyo South District, Kenya. In a cluster-randomized trial from 22 March to 15 April 2012, we randomly allocated five clusters to hotspot-targeted interventions with larviciding, distribution of long-lasting insecticide-treated nets, indoor residual spraying, and focal mass drug administration (2,082 individuals in 432 compounds); five control clusters received malaria control following Kenyan national policy (2,468 individuals in 512 compounds). Our primary outcome measure was parasite prevalence in evaluation zones up to 500 m outside hotspots, determined by nested PCR (nPCR) at baseline and 8 wk (16 June–6 July 2012) and 16 wk (21 August–10 September 2012) post-intervention by technicians blinded to the intervention arm. Secondary outcome measures were parasite prevalence inside hotpots, parasite prevalence in the evaluation zone as a function of distance from the hotspot boundary, Anopheles mosquito density, mosquito breeding site productivity, malaria incidence by passive case detection, and the safety and acceptability of the interventions. Intervention coverage exceeded 87% for all interventions. Hotspot-targeted interventions did not result in a change in nPCR parasite prevalence outside hotspot boundaries (p ≥ 0.187). We observed an average reduction in nPCR parasite prevalence of 10.2% (95% CI −1.3 to 21.7%) inside hotspots 8 wk post

  5. Predictability of Malaria Transmission Intensity in the Mpumalanga Province, South Africa, Using Land Surface Climatology and Autoregressive Analysis

    NASA Technical Reports Server (NTRS)

    Grass, David; Jasinski, Michael F.; Govere, John

    2003-01-01

    There has been increasing effort in recent years to employ satellite remotely sensed data to identify and map vector habitat and malaria transmission risk in data sparse environments. In the current investigation, available satellite and other land surface climatology data products are employed in short-term forecasting of infection rates in the Mpumalanga Province of South Africa, using a multivariate autoregressive approach. The climatology variables include precipitation, air temperature and other land surface states computed by the Off-line Land-Surface Global Assimilation System (OLGA) including soil moisture and surface evaporation. Satellite data products include the Normalized Difference Vegetation Index (NDVI) and other forcing data used in the Goddard Earth Observing System (GEOS-1) model. Predictions are compared to long- term monthly records of clinical and microscopic diagnoses. The approach addresses the high degree of short-term autocorrelation in the disease and weather time series. The resulting model is able to predict 11 of the 13 months that were classified as high risk during the validation period, indicating the utility of applying antecedent climatic variables to the prediction of malaria incidence for the Mpumalanga Province.

  6. Urban and suburban malaria in Rondônia (Brazilian Western Amazon) II. Perennial transmissions with high anopheline densities are associated with human environmental changes.

    PubMed

    Gil, Luiz Herman Soares; Tada, Mauro Shugiro; Katsuragawa, Tony Hiroshi; Ribolla, Paulo Eduardo Martins; da Silva, Luiz Hildebrando Pereira

    2007-06-01

    Longitudinal entomological surveys were performed in Vila Candelária and adjacent rural locality of Bate Estaca concomitantly with a clinical epidemiologic malaria survey. Vila Candelária is a riverside periurban neighborhood of Porto Velho, capital of the state of Rondônia in the Brazilian Amazon. High anopheline densities were found accompanying the peak of rainfall, as reported in rural areas of the region. Moreover, several minor peaks of anophelines were recorded between the end of the dry season and the beginning of the next rainy season. These secondary peaks were related to permanent anopheline breeding sites resulting from human activities. Malaria transmission is, therefore, observed all over the year. In Vila Candelária, the risk of malaria infection both indoors and outdoors was calculated as being 2 and 10/infecting bites per year per inhabitant respectively. Urban malaria in riverside areas was associated with two factors: (1) high prevalence of asymptomatic carriers in a stable human population and (2) high anopheline densities related to human environmental changes. This association is probably found in other Amazonian urban and suburban communities. The implementation of control measures should include environmental sanitation and better characterization of the role of asymptomatic carriers in malaria transmission.

  7. Spatial heterogeneity and temporal evolution of malaria transmission risk in Dakar, Senegal, according to remotely sensed environmental data

    PubMed Central

    2010-01-01

    associated with An. arabiensis densities in Dakar urban setting, which allowed to generate malaria transmission risk maps. The evolution of the risk was quantified, and the results indicated there are benefits of urbanization in Dakar, since the proportion of the low risk population increased while urbanization progressed. PMID:20815867

  8. Rapid Response to Selection, Competitive Release and Increased Transmission Potential of Artesunate-Selected Plasmodium chabaudi Malaria Parasites

    PubMed Central

    Pollitt, Laura C.; Huijben, Silvie; Sim, Derek G.; Salathé, Rahel M.; Jones, Matthew J.; Read, Andrew F.

    2014-01-01

    The evolution of drug resistance, a key challenge for our ability to treat and control infections, depends on two processes: de-novo resistance mutations, and the selection for and spread of resistant mutants within a population. Understanding the factors influencing the rates of these two processes is essential for maximizing the useful lifespan of drugs and, therefore, effective disease control. For malaria parasites, artemisinin-based drugs are the frontline weapons in the fight against disease, but reports from the field of slower parasite clearance rates during drug treatment are generating concern that the useful lifespan of these drugs may be limited. Whether slower clearance rates represent true resistance, and how this provides a selective advantage for parasites is uncertain. Here, we show that Plasmodium chabaudi malaria parasites selected for resistance to artesunate (an artemisinin derivative) through a step-wise increase in drug dose evolved slower clearance rates extremely rapidly. In single infections, these slower clearance rates, similar to those seen in the field, provided fitness advantages to the parasite through increased overall density, recrudescence after treatment and increased transmission potential. In mixed infections, removal of susceptible parasites by drug treatment led to substantial increases in the densities and transmission potential of resistant parasites (competitive release). Our results demonstrate the double-edged sword for resistance management: in our initial selection experiments, no parasites survived aggressive chemotherapy, but after selection, the fitness advantage for resistant parasites was greatest at high drug doses. Aggressive treatment of mixed infections resulted in resistant parasites dominating the pool of gametocytes, without providing additional health benefits to hosts. Slower clearance rates can evolve rapidly and can provide a strong fitness advantage during drug treatment in both single and mixed strain

  9. Rapid response to selection, competitive release and increased transmission potential of artesunate-selected Plasmodium chabaudi malaria parasites.

    PubMed

    Pollitt, Laura C; Huijben, Silvie; Sim, Derek G; Salathé, Rahel M; Jones, Matthew J; Read, Andrew F

    2014-04-01

    The evolution of drug resistance, a key challenge for our ability to treat and control infections, depends on two processes: de-novo resistance mutations, and the selection for and spread of resistant mutants within a population. Understanding the factors influencing the rates of these two processes is essential for maximizing the useful lifespan of drugs and, therefore, effective disease control. For malaria parasites, artemisinin-based drugs are the frontline weapons in the fight against disease, but reports from the field of slower parasite clearance rates during drug treatment are generating concern that the useful lifespan of these drugs may be limited. Whether slower clearance rates represent true resistance, and how this provides a selective advantage for parasites is uncertain. Here, we show that Plasmodium chabaudi malaria parasites selected for resistance to artesunate (an artemisinin derivative) through a step-wise increase in drug dose evolved slower clearance rates extremely rapidly. In single infections, these slower clearance rates, similar to those seen in the field, provided fitness advantages to the parasite through increased overall density, recrudescence after treatment and increased transmission potential. In mixed infections, removal of susceptible parasites by drug treatment led to substantial increases in the densities and transmission potential of resistant parasites (competitive release). Our results demonstrate the double-edged sword for resistance management: in our initial selection experiments, no parasites survived aggressive chemotherapy, but after selection, the fitness advantage for resistant parasites was greatest at high drug doses. Aggressive treatment of mixed infections resulted in resistant parasites dominating the pool of gametocytes, without providing additional health benefits to hosts. Slower clearance rates can evolve rapidly and can provide a strong fitness advantage during drug treatment in both single and mixed strain

  10. Disrupting Mosquito Reproduction and Parasite Development for Malaria Control

    PubMed Central

    Gabrieli, Paolo; Buckee, Caroline O.; Catteruccia, Flaminia

    2016-01-01

    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. PMID:27977810

  11. Asymmetric sound transmission in a passive non-blocking structure with multiple ports

    NASA Astrophysics Data System (ADS)

    Zhu, Yi-Fan; Gu, Zhong-Ming; Liang, Bin; Yang, Jing; Yang, Jun; Yin, Lei-lei; Cheng, Jian-Chun

    2016-09-01

    We present the mechanism for breaking the symmetry in sound transmission between any two neighboring ports in a passive multi-port system. Numerical simulations and experimental measurements verify that by using judiciously designed metastructures to provide an extra wavevector without blocking the sound path, the propagating wave will travel along a preset direction at each port instead of splitting to both directions. We have also demonstrated the flexibility of this scheme to adjust the location of each port. Our design advances further the concept of one-way manipulation in passive two-port systems and may enable novel sound-steering devices for more versatile applications.

  12. Streptococcus pneumoniae Transmission Is Blocked by Type-Specific Immunity in an Infant Mouse Model

    PubMed Central

    Zangari, Tonia; Wang, Yang

    2017-01-01

    ABSTRACT Epidemiological studies on Streptococcus pneumoniae show that rates of carriage are highest in early childhood and that the major benefit of the pneumococcal conjugate vaccine (PCV) is a reduction in the incidence of nasopharyngeal colonization through decreased transmission within a population. In this study, we sought to understand how anti-S. pneumoniae immunity affects nasal shedding of bacteria, the limiting step in experimental pneumococcal transmission. Using an infant mouse model, we examined the role of immunity (passed from mother to pup) on shedding and within-litter transmission of S. pneumoniae by pups infected at 4 days of life. Pups from both previously colonized immune and PCV-vaccinated mothers had higher levels of anti-S. pneumoniae IgG than pups from non-immune or non-vaccinated mothers and shed significantly fewer S. pneumoniae over the first 5 days of infection. By setting up cross-foster experiments, we demonstrated that maternal passage of antibody to pups either in utero or post-natally decreases S. pneumoniae shedding. Passive immunization experiments showed that type-specific antibody to capsular polysaccharide is sufficient to decrease shedding and that the agglutinating function of immunoglobulin is required for this effect. Finally, we established that anti-pneumococcal immunity and anti-PCV vaccination block host-to-host transmission of S. pneumoniae. Moreover, immunity in either the donor or recipient pups alone was sufficient to reduce rates of transmission, indicating that decreased shedding and protection from acquisition of colonization are both contributing factors. Our findings provide a mechanistic explanation for the reduced levels of S. pneumoniae transmission between hosts immune from prior exposure and among vaccinated children. PMID:28292980

  13. Sickle cell trait (HbAS) and stunting in children below two years of age in an area of high malaria transmission

    PubMed Central

    Kreuels, Benno; Ehrhardt, Stephan; Kreuzberg, Christina; Adjei, Samuel; Kobbe, Robin; Burchard, Gerd D; Ehmen, Christa; Ayim, Matilda; Adjei, Ohene; May, Jürgen

    2009-01-01

    Background While the protective effects of sickle cell trait (HbAS) against severe malaria and the resulting survival advantage are well known, the impact on the physical development in young children remains unclear. This study was aimed to investigate the relationship between HbS carriage and stunting in children below two years of age in a cohort from the Ashanti Region, Ghana. Methods 1,070 children were recruited at three months of age and followed-up for 21 months with anthropometric measurements performed every three months. Incidence rate ratios with 95% confidence intervals were calculated by Poisson regression to estimate the association of β-globin genotypes with the number of malaria episodes. Odds ratios (OR) were calculated for the association between the occurrence of β-globin genotypes and/or malaria episodes and stunting. The age-dependent between-group and within-group effects for the β-globin genotypes were assessed by population-averaged models estimated by generalized estimation equation with autoregressive correlation structure. Results Analyses showed a significantly lower age-dependent risk of stunting (OR 0.56; 95% CI 0.33–0.96) in carriers of the HbAS genotype (n = 102) in comparison to those with HbAA (n = 692). This effect was restricted to children who experienced malaria episodes during the observation period suggesting that the beneficial effect of the β-globin HbS variant on the incidence of stunting is closely linked to its protection from mild malaria episodes. Conclusion The lower risk of chronic malnutrition in early childhood, mediated by protection against mild malaria episodes, may contribute to the survival advantage of HbAS carriers in areas of high malaria transmission. PMID:19149873

  14. Plasmodium falciparum malaria in the Peruvian Amazon, a region of low transmission, is associated with immunologic memory.

    PubMed

    Clark, Eva H; Silva, Claudia J; Weiss, Greta E; Li, Shanping; Padilla, Carlos; Crompton, Peter D; Hernandez, Jean N; Branch, OraLee H

    2012-04-01

    The development of clinical immunity to Plasmodium falciparum malaria is thought to require years of parasite exposure, a delay often attributed to difficulties in developing protective antibody levels. In this study, we evaluated several P. falciparum vaccine candidate antigens, including apical membrane antigen 1 (AMA-1), circumsporozoite protein (CSP), erythrocyte binding antigen 175 (EBA-175), and the 19-kDa region of merozoite surface protein 1 (MSP1(19)). After observing a more robust antibody response to MSP1(19), we evaluated the magnitude and longevity of IgG responses specific to this antigen in Peruvian adults and children before, during, and after P. falciparum infection. In this low-transmission region, even one reported prior infection was sufficient to produce a positive anti-MSP1(19) IgG response for >5 months in the absence of reinfection. We also observed an expansion of the total plasmablast (CD19(+) CD27(+) CD38(high)) population in the majority of individuals shortly after infection and detected MSP1-specific memory B cells in a subset of individuals at various postinfection time points. This evidence supports our hypothesis that effective antimalaria humoral immunity can develop in low-transmission regions.

  15. A malaria vaccine for travelers and military personnel: Requirements and top candidates.

    PubMed

    Teneza-Mora, Nimfa; Lumsden, Joanne; Villasante, Eileen

    2015-12-22

    Malaria remains an important health threat to non-immune travelers with the explosive growth of global travel. Populations at high risk of acquiring malaria infections include once semi-immune travelers who visit friends and relatives, military forces, business travelers and international tourists with destinations to sub-Saharan Africa, where malaria transmission intensity is high. Most malaria cases have been associated with poor compliance with existing preventive measures, including chemoprophylaxis. High risk groups would benefit immensely from an efficacious vaccine to protect them against malaria infection and together make up a sizable market for such a vaccine. The attributes of an ideal malaria vaccine for non-immune travelers and military personnel include a protective efficacy of 80% or greater, durability for at least 6 months, an acceptable safety profile and compatibility with existing preventive measures. It is very likely that a malaria vaccine designed to effectively prevent infection and clinical disease in the non-immune traveler and military personnel will also protect semi-immune residents of malaria-endemic areas and contribute to malaria elimination by reducing or blocking malaria transmission. The RTS,S vaccine (GlaxoSmithKline) and the PfSPZ Vaccine (Sanaria Inc) are the leading products that would make excellent vaccine candidates for these vulnerable populations.

  16. Malaria in pregnant women living in areas of low transmission on the southeast Brazilian Coast: molecular diagnosis and humoural immunity profile

    PubMed Central

    Hristov, Angélica Domingues; Sanchez, Maria Carmen Arroyo; Ferreira, José Jarbas Bittencourt; Lima, Giselle Fernandes Maciel de Castro; Inoue, Juliana; Costa-Nascimento, Maria de Jesus; Sanchez, Arianni Rondelli; Ramos-Sanchez, Eduardo Milton; Santi, Silvia Maria Di

    2014-01-01

    Studies on autochthonous malaria in low-transmission areas in Brazil have acquired epidemiological relevance because they suggest continued transmission in what remains of the Atlantic Forest. In the southeastern portion of the state of São Paulo, outbreaks in the municipality of Juquitiba have been the focus of studies on the prevalence of Plasmodium, including asymptomatic cases. Data on the occurrence of the disease or the presence of antiplasmodial antibodies in pregnant women from this region have not previously been described. Although Plasmodium falciparum in pregnant women has been widely addressed in the literature, the interaction of Plasmodium vivax and Plasmodium malariae with this cohort has been poorly explored to date. We monitored the circulation of Plasmodium in pregnant women in health facilities located in Juquitiba using thick blood film and molecular protocols, as well as immunological assays, to evaluate humoural immune parameters. Through real-time and nested polymerase chain reaction, P. vivax and P. malariae were detected for the first time in pregnant women, with a positivity of 5.6%. Immunoassays revealed the presence of IgG antibodies: 44% for ELISA-Pv, 38.4% for SD-Bioline-Pv and 18.4% for indirect immunofluorescence assay-Pm. The high prevalence of antibodies showed significant exposure of this population to Plasmodium. In regions with similar profiles, testing for a malaria diagnosis might be indicated in prenatal care. PMID:25494466

  17. Dynasore blocks evoked release while augmenting spontaneous synaptic transmission from primary visceral afferents.

    PubMed

    Hofmann, Mackenzie E; Andresen, Michael C

    2017-01-01

    The recycling of vesicle membrane fused during exocytosis is essential to maintaining neurotransmission. The GTPase dynamin is involved in pinching off membrane to complete endocytosis and can be inhibited by dynasore resulting in activity-dependent depletion of release-competent synaptic vesicles. In rat brainstem slices, we examined the effects of dynasore on three different modes of glutamate release-spontaneous, evoked, and asynchronous release-at solitary tract (ST) inputs to neurons in the nucleus of the solitary tract (NTS). Intermittent bursts of stimuli to the ST interspersed with pauses in stimulation allowed examination of these three modes in each neuron continuously. Application of 100 μM dynasore rapidly increased the spontaneous EPSC (sEPSC) frequency which was followed by inhibition of both ST-evoked EPSCs (ST-EPSC) as well as asynchronous EPSCs. The onset of ST-EPSC failures was not accompanied by amplitude reduction-a pattern more consistent with conduction block than reduced probability of vesicle release. Neither result suggested that dynasore interrupted endocytosis. The dynasore response profile resembled intense presynaptic TRPV1 activation. The TRPV1 antagonist capsazepine failed to prevent dynasore increases in sEPSC frequency but did prevent the block of the ST-EPSC. In contrast, the TRPV1 antagonist JNJ 17203212 prevented both actions of dynasore in neurons with TRPV1-expressing ST inputs. In a neuron lacking TRPV1-expressing ST inputs, however, dynasore promptly increased sEPSC rate followed by block of ST-evoked EPSCs. Together our results suggest that dynasore actions on ST-NTS transmission are TRPV1-independent and changes in glutamatergic transmission are not consistent with changes in vesicle recycling and endocytosis.

  18. Dynasore blocks evoked release while augmenting spontaneous synaptic transmission from primary visceral afferents

    PubMed Central

    Andresen, Michael C.

    2017-01-01

    The recycling of vesicle membrane fused during exocytosis is essential to maintaining neurotransmission. The GTPase dynamin is involved in pinching off membrane to complete endocytosis and can be inhibited by dynasore resulting in activity-dependent depletion of release-competent synaptic vesicles. In rat brainstem slices, we examined the effects of dynasore on three different modes of glutamate release–spontaneous, evoked, and asynchronous release–at solitary tract (ST) inputs to neurons in the nucleus of the solitary tract (NTS). Intermittent bursts of stimuli to the ST interspersed with pauses in stimulation allowed examination of these three modes in each neuron continuously. Application of 100 μM dynasore rapidly increased the spontaneous EPSC (sEPSC) frequency which was followed by inhibition of both ST-evoked EPSCs (ST-EPSC) as well as asynchronous EPSCs. The onset of ST-EPSC failures was not accompanied by amplitude reduction–a pattern more consistent with conduction block than reduced probability of vesicle release. Neither result suggested that dynasore interrupted endocytosis. The dynasore response profile resembled intense presynaptic TRPV1 activation. The TRPV1 antagonist capsazepine failed to prevent dynasore increases in sEPSC frequency but did prevent the block of the ST-EPSC. In contrast, the TRPV1 antagonist JNJ 17203212 prevented both actions of dynasore in neurons with TRPV1-expressing ST inputs. In a neuron lacking TRPV1-expressing ST inputs, however, dynasore promptly increased sEPSC rate followed by block of ST-evoked EPSCs. Together our results suggest that dynasore actions on ST-NTS transmission are TRPV1-independent and changes in glutamatergic transmission are not consistent with changes in vesicle recycling and endocytosis. PMID:28358887

  19. a Modal Expansion Analysis of Noise Transmission Through Circular Cylindrical Shell Structures with Blocking Masses

    NASA Astrophysics Data System (ADS)

    GARDONIO, P.; FERGUSON, N. S.; FAHY, F. J.

    2001-07-01

    This paper covers the development and application of a modal interaction analysis (MIA) to investigate the plane wave transmission characteristics of a circular cylindrical sandwich shell of the type used in the aerospace industry for satellite launch vehicles. The model is capable of handling many high order structural and acoustic modes, and can be used to investigate the sensitivity to different structural stiffness configurations, angles of incidence, damping and cavity absorption. The model has been developed to predict the structural response and transmitted noise when a number of discrete masses are applied to the shell. The study presented considers a set of cases where blocking masses, having a total weight equal to 8% of the cylinder weight, are attached to the cylinder. The simulations carried out show a substantial reduction of the sound transmission in many of the first 15 one-third octave frequency bands (frequency range 22·4-707 Hz). The blocking masses act on the shape of the cylinder normal modes and their orientations with respect to the plane of the incident wavenumber vector. In particular, the circumferential re-orientation reduces the coupling between the incident acoustic field and the structural modes of the cylinder. The modification of the structural mode shapes, both in axial and circumferential directions, also reduces the coupling between the cylinder modes and the acoustic modes of the interior.Simulations show the effect of the number of structural and acoustic modes included on the calculated frequency response, and indicate the number necessary for an accurate prediction of the resonant and non-resonant sound transmission through the structure. In particular, the effect of neglecting off-resonance acoustic and structural modes is investigated. It is shown that restricting the acoustic and structural modes to those having natural frequencies within an interval of ±40 and ±60 Hz, respectively, of the excitation frequency produces

  20. Homology blocks of Plasmodium falciparum var genes and clinically distinct forms of severe malaria in a local population

    PubMed Central

    2013-01-01

    Background The primary target of the human immune response to the malaria parasite Plasmodium falciparum, P. falciparum erythrocyte membrane protein 1 (PfEMP1), is encoded by the members of the hyper-diverse var gene family. The parasite exhibits antigenic variation via mutually exclusive expression (switching) of the ~60 var genes within its genome. It is thought that different variants exhibit different host endothelial binding preferences that in turn result in different manifestations of disease. Results Var sequences comprise ancient sequence fragments, termed homology blocks (HBs), that recombine at exceedingly high rates. We use HBs to define distinct var types within a local population. We then reanalyze a dataset that contains clinical and var expression data to investigate whether the HBs allow for a description of sequence diversity corresponding to biological function, such that it improves our ability to predict disease phenotype from parasite genetics. We find that even a generic set of HBs, which are defined for a small number of non-local parasites: capture the majority of local sequence diversity; improve our ability to predict disease severity from parasite genetics; and reveal a previously hypothesized yet previously unobserved parasite genetic basis for two forms of severe disease. We find that the expression rates of some HBs correlate more strongly with severe disease phenotypes than the expression rates of classic var DBLα tag types, and principal components of HB expression rate profiles further improve genotype-phenotype models. More specifically, within the large Kenyan dataset that is the focus of this study, we observe that HB expression differs significantly for severe versus mild disease, and for rosetting versus impaired consciousness associated severe disease. The analysis of a second much smaller dataset from Mali suggests that these HB-phenotype associations are consistent across geographically distant populations, since we find

  1. The Rheopathobiology of Plasmodium vivax and Other Important Primate Malaria Parasites.

    PubMed

    Russell, Bruce M; Cooke, Brian M

    2017-04-01

    Our current understanding of how malaria parasites remodel their host red blood cells (RBCs) and ultimately cause disease is largely based on studies of Plasmodium falciparum. In this review, we expand our knowledge to include what is currently known about pathophysiological changes to RBCs that are infected by non-falciparum malaria parasites. We highlight the potential folly of making generalizations about the rheology of malaria infection, and emphasize the need for more systematic studies into the erythrocytic biology of non-falciparum malaria parasites. We propose that a better understanding of the mechanisms that underlie the changes to RBCs induced by malaria parasites other than P. falciparum may be highly informative for the development of therapeutics that specifically disrupt the altered rheological profile of RBCs infected with either sexual- or asexual-stage parasites, resulting in drugs that block transmission, reduce disease severity, and help delay the onset of resistance to current and future anti-malaria drugs.

  2. Early-phase transmission of Yersinia pestis by unblocked Xenopsylla cheopis (Siphonaptera: Pulicidae) is as efficient as transmission by blocked fleas.

    PubMed

    Eisen, Rebecca J; Wilder, Aryn P; Bearden, Scott W; Montenieri, John A; Gage, Kenneth L

    2007-07-01

    For almost a century, the oriental rat flea, Xenopsylla cheopis (Rothschild) (Siphonaptera: Pulicidae), was thought to be the most efficient vector of the plague bacterium Yersinia pestis (Yersin). Approximately 2 wk after consuming an infectious bloodmeal, a blockage often forms in the flea's proventriculus, which forces the flea to increase its biting frequency and consequently increases the likelihood of transmission. However, if fleas remain blocked and continue to feed, they usually die within 5 d of blocking, resulting in a short infectious window. Despite observations of X. cheopis transmitting Y. pestis shortly after pathogen acquisition, early-phase transmission (e.g., transmission 1-4 d postinfection [ p.i.]) by unblocked fleas was viewed as anomalous and thought to occur only by mass action. We used an artificial feeding system to infect colony-reared X. cheopis with a fully virulent strain of Y. pestis, and we evaluated transmission efficiency 1- 4 d p.i. We demonstrate 1) that a single infected and unblocked X. cheopis can infect a susceptible host as early as 1 d p.i., 2) the number of fleas per host required for unblocked fleas to drive a plague epizootic by early-phase transmission is within the flea infestation range observed in nature, and 3) early-phase transmission by unblocked fleas in the current study was at least as efficient as transmission by blocked fleas in a previously published study using the same colony of fleas and same bacterial strain. Furthermore, transmission efficiency seemed to remain constant until block formation, resulting in an infectious period considerably longer than previously thought.

  3. Accelerating to Zero: Strategies to Eliminate Malaria in the Peruvian Amazon

    PubMed Central

    Quispe, Antonio M.; Llanos-Cuentas, Alejandro; Rodriguez, Hugo; Clendenes, Martin; Cabezas, Cesar; Leon, Luis M.; Chuquiyauri, Raul; Moreno, Marta; Kaslow, David C.; Grogl, Max; Herrera, Sócrates; Magill, Alan J.; Kosek, Margaret; Vinetz, Joseph M.; Lescano, Andres G.; Gotuzzo, Eduardo

    2016-01-01

    In February 2014, the Malaria Elimination Working Group, in partnership with the Peruvian Ministry of Health (MoH), hosted its first international conference on malaria elimination in Iquitos, Peru. The 2-day meeting gathered 85 malaria experts, including 18 international panelists, 23 stakeholders from different malaria-endemic regions of Peru, and 11 MoH authorities. The main outcome was consensus that implementing a malaria elimination project in the Amazon region is achievable, but would require: 1) a comprehensive strategic plan, 2) the altering of current programmatic guidelines from control toward elimination by including symptomatic as well as asymptomatic individuals for antimalarial therapy and transmission-blocking interventions, and 3) the prioritization of community-based active case detection with proper rapid diagnostic tests to interrupt transmission. Elimination efforts must involve key stakeholders and experts at every level of government and include integrated research activities to evaluate, implement, and tailor sustainable interventions appropriate to the region.

  4. Effects of insecticide-treated bednets during early infancy in an African area of intense malaria transmission: a randomized controlled trial.

    PubMed Central

    Müller, Olaf; Traoré, Corneille; Kouyaté, Bocar; Yé, Yazoumé; Frey, Claudia; Coulibaly, Boubacar; Becher, Heiko

    2006-01-01

    OBJECTIVE: Insecticide-impregnated bednets and curtains have been shown by many studies to be effective against malaria. However, because of possible interactions with immunity development, treated bednets may cause no effect at all or even an increase in malaria morbidity and mortality in areas of high transmission. To clarify this issue, we did a randomized controlled trial to assess the long-term effects of bednet protection during early infancy. METHODS: A total of 3387 neonates from 41 villages in rural Burkina Faso were individually randomized to receive either bednet protection from birth (group A) or from age 6 months (group B). Primary outcomes were all-cause mortality in all study children and incidence of falciparum malaria in a representative subsample of the study population. FINDINGS: After a mean follow-up of 27 months, there were 129 deaths in group A and 128 deaths in group B rate ratio (RR) 1.0 (95% confidence interval (CI): 0.78-1.27)). Falciparum malaria incidence was lower in group A than in group B, during early (0-5 months) and late infancy (6-12 months) (RR 3.1, 95% CI: 2.0-4.9; RR 1.3, 95% CI: 1.1-1.6) and rates of moderate to severe anaemia were significantly lower during late infancy (11.5% vs 23.3%, P = 0.008), but there were no differences between groups in these parameters in children older than 12 months. CONCLUSION: The findings from this study provide additional evidence for the efficacy of insecticide-treated nets in young children living in areas of intense malaria transmission. PMID:16501729

  5. Block Transmissions over Doubly Selective Channels: Iterative Channel Estimation and Turbo Equalization

    NASA Astrophysics Data System (ADS)

    Fang, Kun; Rugini, Luca; Leus, Geert

    2010-12-01

    Modern wireless communication systems require high transmission rates, giving rise to frequency selectivity due to multipath propagation. In addition, high-mobility terminals and scatterers induce Doppler shifts that introduce time selectivity. Therefore, advanced techniques are needed to accurately model the time- and frequency-selective (i.e., doubly selective) channels and to counteract the related performance degradation. In this paper, we develop new receivers for orthogonal frequency-division multiplexing (OFDM) systems and single-carrier (SC) systems in doubly selective channels by embedding the channel estimation task within low-complexity block turbo equalizers. Linear minimum mean-squared error (MMSE) pilot-assisted channel estimators are presented, and the soft data estimates from the turbo equalizers are used to improve the quality of the channel estimates.

  6. Assessment of a remote sensing-based model for predicting malaria transmission risk in villages of Chiapas, Mexico

    NASA Technical Reports Server (NTRS)

    Beck, L. R.; Rodriguez, M. H.; Dister, S. W.; Rodriguez, A. D.; Washino, R. K.; Roberts, D. R.; Spanner, M. A.

    1997-01-01

    A blind test of two remote sensing-based models for predicting adult populations of Anopheles albimanus in villages, an indicator of malaria transmission risk, was conducted in southern Chiapas, Mexico. One model was developed using a discriminant analysis approach, while the other was based on regression analysis. The models were developed in 1992 for an area around Tapachula, Chiapas, using Landsat Thematic Mapper (TM) satellite data and geographic information system functions. Using two remotely sensed landscape elements, the discriminant model was able to successfully distinguish between villages with high and low An. albimanus abundance with an overall accuracy of 90%. To test the predictive capability of the models, multitemporal TM data were used to generate a landscape map of the Huixtla area, northwest of Tapachula, where the models were used to predict risk for 40 villages. The resulting predictions were not disclosed until the end of the test. Independently, An. albimanus abundance data were collected in the 40 randomly selected villages for which the predictions had been made. These data were subsequently used to assess the models' accuracies. The discriminant model accurately predicted 79% of the high-abundance villages and 50% of the low-abundance villages, for an overall accuracy of 70%. The regression model correctly identified seven of the 10 villages with the highest mosquito abundance. This test demonstrated that remote sensing-based models generated for one area can be used successfully in another, comparable area.

  7. Chemotherapy of drug-resistant malaria

    PubMed Central

    Kain, Kevin C

    1996-01-01

    OBJECTIVE: To review the impact of drug-resistant malaria on current management of plasmodial infections. DATA SOURCES: A MEDLINE search of the English-language medical literature from 1985 to 1995; bibliographies of selected papers; international malaria advisory experts. DATA SYNTHESIS: Combinations of artemisinin derivatives and mefloquine or atovaquone plus proguanil appear to be the most active drug regimens against multidrug-resistant falciparum malaria from Southeast Asia. The optimal therapy for chloroquine-resistant Plasmodium vivax is unknown, but recent data indicate that halofantrine or chloroquine plus high doses of primaquine are efficacious. CONCLUSIONS: The incidence of drug-resistant malaria continues to increase at a rate that exceeds new drug development. Ultimately the control of malaria will require more creative approaches than just the development of additional inhibitory drugs. These might include the identification of biochemical pathways unique to the parasite (such as drug efflux and heme polymerization), making it possible to design new classes of antimalarial agents that are selectively toxic to the parasite; methods to block parasite development in the mosquito vector; and multistage vaccines against asexual and sexual stages to block both the pathophysiology and the transmission of disease. PMID:22514413

  8. Secure transmission of images based on chaotic systems and cipher block chaining

    NASA Astrophysics Data System (ADS)

    Lakhani, Mahdieh Karimi; Behnam, Hamid; Karimi, Arash

    2013-01-01

    The ever-growing penetration of communication networks, digital and Internet technologies in our everyday lives has the transmission of text data, as well as multimedia data such as images and videos, possible. Digital images have a vast usage in a number of applications, including medicine and providing security authentication, for example. This applicability becomes evident when images, such as walking or people's facial features, are utilized in their identification. Considering the required security level and the properties of images, different algorithms may be used. After key generation using logistic chaos signals, a scrambling function is utilized for image agitation in both horizontal and vertical axes, and then a block-chaining mode of operation may be applied to encrypt the resultant image. The results demonstrate that using the proposed method drastically degrades the correlation between the image components and also the entropy is increased to an acceptable level. Therefore, the image will become greatly resistant to differential attacks. However, the increasing scrambling rounds and the decreasing number of bits of the blocks result in increasing the entropy and decreasing the correlation.

  9. High Plasmodium falciparum longitudinal prevalence is associated with high multiclonality and reduced clinical malaria risk in a seasonal transmission area of Mali

    PubMed Central

    Adomako-Ankomah, Yaw; Chenoweth, Matthew S.; Durfee, Katelyn; Doumbia, Saibou; Konate, Drissa; Doumbouya, Mory; Keita, Abdoul S.; Nikolaeva, Daria; Tullo, Gregory S.; Anderson, Jennifer M.; Fairhurst, Rick M.; Daniels, Rachel; Volkman, Sarah K.; Diakite, Mahamadou; Long, Carole A.

    2017-01-01

    The effects of persistent Plasmodium falciparum (Pf) infection and multiclonality on subsequent risk of clinical malaria have been reported, but the relationship between these 2 parameters and their relative impacts on the clinical outcome of infection are not understood. A longitudinal cohort study was conducted in a seasonal and high-transmission area of Mali, in which 500 subjects aged 1–65 years were followed for 1 year. Blood samples were collected every 2 weeks, and incident malaria cases were diagnosed and treated. Pf infection in each individual at each time point was assessed by species-specific nested-PCR, and Pf longitudinal prevalence per person (PfLP, proportion of Pf-positive samples over 1 year) was calculated. Multiclonality of Pf infection was measured using a 24-SNP DNA barcoding assay at 4 time-points (two in wet season, and two in dry season) over one year. PfLP was positively correlated with multiclonality at each time point (all r≥0.36; all P≤0.011). When host factors (e.g., age, gender), PfLP, and multiclonality (at the beginning of the transmission season) were analyzed together, only increasing age and high PfLP were associated with reduced clinical malaria occurrence or reduced number of malaria episodes (for both outcomes, P<0.001 for age, and P = 0.005 for PfLP). When age, PfLP and baseline Pf positivity were analyzed together, the effect of high PfLP remained significant even after adjusting for the other two factors (P = 0.001 for malaria occurrence and P<0.001 for number of episodes). In addition to host age and baseline Pf positivity, both of which have been reported as important modifiers of clinical malaria risk, our results demonstrate that persistent parasite carriage, but not baseline multiclonality, is associated with reduced risk of clinical disease in this population. Our study emphasizes the importance of considering repeated parasite exposure in future studies that evaluate clinical malaria risk. PMID:28158202

  10. High Plasmodium falciparum longitudinal prevalence is associated with high multiclonality and reduced clinical malaria risk in a seasonal transmission area of Mali.

    PubMed

    Adomako-Ankomah, Yaw; Chenoweth, Matthew S; Durfee, Katelyn; Doumbia, Saibou; Konate, Drissa; Doumbouya, Mory; Keita, Abdoul S; Nikolaeva, Daria; Tullo, Gregory S; Anderson, Jennifer M; Fairhurst, Rick M; Daniels, Rachel; Volkman, Sarah K; Diakite, Mahamadou; Miura, Kazutoyo; Long, Carole A

    2017-01-01

    The effects of persistent Plasmodium falciparum (Pf) infection and multiclonality on subsequent risk of clinical malaria have been reported, but the relationship between these 2 parameters and their relative impacts on the clinical outcome of infection are not understood. A longitudinal cohort study was conducted in a seasonal and high-transmission area of Mali, in which 500 subjects aged 1-65 years were followed for 1 year. Blood samples were collected every 2 weeks, and incident malaria cases were diagnosed and treated. Pf infection in each individual at each time point was assessed by species-specific nested-PCR, and Pf longitudinal prevalence per person (PfLP, proportion of Pf-positive samples over 1 year) was calculated. Multiclonality of Pf infection was measured using a 24-SNP DNA barcoding assay at 4 time-points (two in wet season, and two in dry season) over one year. PfLP was positively correlated with multiclonality at each time point (all r≥0.36; all P≤0.011). When host factors (e.g., age, gender), PfLP, and multiclonality (at the beginning of the transmission season) were analyzed together, only increasing age and high PfLP were associated with reduced clinical malaria occurrence or reduced number of malaria episodes (for both outcomes, P<0.001 for age, and P = 0.005 for PfLP). When age, PfLP and baseline Pf positivity were analyzed together, the effect of high PfLP remained significant even after adjusting for the other two factors (P = 0.001 for malaria occurrence and P<0.001 for number of episodes). In addition to host age and baseline Pf positivity, both of which have been reported as important modifiers of clinical malaria risk, our results demonstrate that persistent parasite carriage, but not baseline multiclonality, is associated with reduced risk of clinical disease in this population. Our study emphasizes the importance of considering repeated parasite exposure in future studies that evaluate clinical malaria risk.

  11. Malaria parasite development in mosquitoes.

    PubMed

    Beier, J C

    1998-01-01

    Mosquitoes of the genus Anopheles transmit malaria parasites to humans. Anopheles mosquito species vary in their vector potential because of environmental conditions and factors affecting their abundance, blood-feeding behavior, survival, and ability to support malaria parasite development. In the complex life cycle of the parasite in female mosquitoes, a process termed sporogony, mosquitoes acquire gametocyte-stage parasites from blood-feeding on an infected host. The parasites carry out fertilization in the midgut, transform to ookinetes, then oocysts, which produce sporozoites. Sporozoites invade the salivary glands and are transmitted when the mosquito feeds on another host. Most individual mosquitoes that ingest gametocytes do not support development to the sporozoite stage. Bottle-necks occur at every stage of the cycle in the mosquito. Powerful new techniques and approaches exist for evaluating malaria parasite development and for identifying mechanisms regulating malaria parasite-vector interactions. This review focuses on those interactions that are important for the development of new approaches for evaluating and blocking transmission in nature.

  12. Optical, UV and soft x-ray transmission of optical blocking layer for the x-ray CCD

    NASA Astrophysics Data System (ADS)

    Kawai, K.; Kohmura, T.; Ikeda, S.; Kaneko, K.; watanabe, T.; Tsunemi, H.; Hayashida, K.; Anabuki, N.; Nakajima, H.; Ueda, S.; Tsuru, T. G.; Dotani, T.; Ozaki, M.; Matsuta, K.; Fujinaga, T.; Kitamoto, S.; Murakami, H.; Hiraga, J.; Mori, K.; ASTRO-H SXI Team

    2012-03-01

    We have newly developed the back-illuminated (BI)-CCD which has an Optical Blocking Layer (OBL) directly coating its X-ray illumination surface with Aluminum-Polyimide-Aluminum instead of Optical Blocking Filter (OBF). OBL is composed of a thin polyimide layer sandwiched by two Al layers. Al and Polyimide has a capability to cut visible light and EUV, respectively. To evaluate the performance of OBL that cut off EUV as well as transmit soft X-ray, we measured the EUV and Soft X-ray transmission of both OBL at various energy range between 15-2000 eV by utilizing beam line located at the Photon Factory in High Energy Accelerator Research Organization. We obtained the EUV transmission to be ~3% at 41eV which is as same as expected transmission from the designed thickness of polyimide layer, and found no significant change of the EUV transmission of polyimide found during 9month. We also obtained the Soft X-ray transmission of OBL, and found the X-ray transmission of OBL was consistent with the result expected from the thickness of OBL. We also measured the Optical transmission of OBL between 500-900 nm to evaluate the performance of Al that cut off optical light, and obtained the optical transmission to be less than 4×10-5.

  13. A global assessment of closed forests, deforestation and malaria risk.

    PubMed

    Guerra, C A; Snow, R W; Hay, S I

    2006-04-01

    Global environmental change is expected to affect profoundly the transmission of the parasites that cause human malaria. Amongst the anthropogenic drivers of change, deforestation is arguably the most conspicuous, and its rate is projected to increase in the coming decades. The canonical epidemiological understanding is that deforestation increases malaria risk in Africa and the Americas and diminishes it in South-east Asia. Partial support for this position is provided here, through a systematic review of the published literature on deforestation, malaria and the relevant vector bionomics. By using recently updated boundaries for the spatial limits of malaria and remotely-sensed estimates of tree cover, it has been possible to determine the population at risk of malaria in closed forest, at least for those malaria-endemic countries that lie within the main blocks of tropical forest. Closed forests within areas of malaria risk cover approximately 1.5 million km2 in the Amazon region, 1.4 million km2 in Central Africa, 1.2 million km2 in the Western Pacific, and 0.7 million km2 in South-east Asia. The corresponding human populations at risk of malaria within these forests total 11.7 million, 18.7 million, 35.1 million and 70.1 million, respectively. By coupling these numbers with the country-specific rates of deforestation, it has been possible to rank malaria-endemic countries according to their potential for change in the population at risk of malaria, as the result of deforestation. The on-going research aimed at evaluating these relationships more quantitatively, through the Malaria Atlas Project (MAP), is highlighted.

  14. A global assessment of closed forests, deforestation and malaria risk

    PubMed Central

    GUERRA, C. A.; SNOW, R. W.; HAY, S. I.

    2011-01-01

    Global environmental change is expected to affect profoundly the transmission of the parasites that cause human malaria. Amongst the anthropogenic drivers of change, deforestation is arguably the most conspicuous, and its rate is projected to increase in the coming decades. The canonical epidemiological understanding is that deforestation increases malaria risk in Africa and the Americas and diminishes it in South–east Asia. Partial support for this position is provided here, through a systematic review of the published literature on deforestation, malaria and the relevant vector bionomics. By using recently updated boundaries for the spatial limits of malaria and remotely-sensed estimates of tree cover, it has been possible to determine the population at risk of malaria in closed forest, at least for those malaria-endemic countries that lie within the main blocks of tropical forest. Closed forests within areas of malaria risk cover approximately 1.5 million km2 in the Amazon region, 1.4 million km2 in Central Africa, 1.2 million km2 in the Western Pacific, and 0.7 million km2 in South–east Asia. The corresponding human populations at risk of malaria within these forests total 11.7 million, 18.7 million, 35.1 million and 70.1 million, respectively. By coupling these numbers with the country-specific rates of deforestation, it has been possible to rank malaria-endemic countries according to their potential for change in the population at risk of malaria, as the result of deforestation. The on-going research aimed at evaluating these relationships more quantitatively, through the Malaria Atlas Project (MAP), is highlighted. PMID:16630376

  15. Breast Milk as a Potential Source of Epstein-Barr Virus Transmission Among Infants Living in a Malaria-Endemic Region of Kenya

    PubMed Central

    Daud, Ibrahim I.; Coleman, Carrie B.; Smith, Nicholas A.; Ogolla, Sidney; Simbiri, Kenneth; Bukusi, Elizabeth A.; Ng'ang'a, Zipporah W.; Sumba, Peter O.; Vulule, John; Ploutz-Snyder, Robert; Dent, Arlene E.; Rochford, Rosemary

    2015-01-01

    Background. We previously reported that infants in Kenya were infected with Epstein-Barr virus (EBV) at <6 months of age, suggesting that mothers were the likely source of transmissible virus to the infant. In this study, we investigated whether breast milk contained infectious EBV and the role of malaria in EBV shedding in breast milk. Methods. Breast milk samples were obtained from Kenyan mothers at postpartum weeks 6, 10, 14, and 18 and analyzed for presence of infectious EBV. Results. We found that the prevalence of EBV DNA and the mean EBV load were significantly higher at 6 weeks and decreased through postpartum week 18 (P < .0001). High EBV load in breast milk correlated with mothers who had Plasmodium falciparum malaria at delivery. To determine whether viral DNA was encapsidated, breast milk samples were treated with DNAse before DNA extraction. Sixty percent of samples were DNAse resistant, suggesting that the viral DNA in breast milk was encapsidated. Next, we exposed peripheral blood mononuclear cells to breast milk supernatant, which resulted in the generation of EBV-positive lymphoblastoid cell lines, indicating that the virus in breast milk was infectious. Conclusions. Our data suggest that breast milk contains infectious EBV and is a potential source of viral transmission to infants living in malaria-endemic regions. PMID:25985902

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

    PubMed Central

    Kasashima, Katsumi; Sezutsu, Hideki; Matsuoka, Hiroyuki

    2016-01-01

    Malaria is an important global public health challenge, and is transmitted by anopheline mosquitoes during blood feeding. Mosquito vector control is one of the most effective methods to control malaria, and population replacement with genetically engineered mosquitoes to block its transmission is expected to become a new vector control strategy. The salivary glands are an effective target tissue for the expression of molecules that kill or inactivate malaria parasites. Moreover, salivary gland cells express a large number of molecules that facilitate blood feeding and parasite transmission to hosts. In the present study, we adapted a functional deficiency system in specific tissues by inducing cell death using the mouse Bcl-2-associated X protein (Bax) to the Asian malaria vector mosquito, Anopheles stephensi. We applied this technique to salivary gland cells, and produced a transgenic strain containing extremely low amounts of saliva. Although probing times for feeding on mice were longer in transgenic mosquitoes than in wild-type mosquitoes, transgenic mosquitoes still successfully ingested blood. Transgenic mosquitoes also exhibited a significant reduction in oocyst formation in the midgut in a rodent malaria model. These results indicate that mosquito saliva plays an important role in malaria infection in the midgut of anopheline mosquitoes. The dysfunction in the salivary glands enabled the inhibition of malaria transmission from hosts to mosquito midguts. Therefore, salivary components have potential in the development of new drugs or genetically engineered mosquitoes for malaria control. PMID:27598328

  17. Fine-Scale Mapping by Spatial Risk Distribution Modeling for Regional Malaria Endemicity and Its Implications under the Low-to-Moderate Transmission Setting in Western Cambodia

    PubMed Central

    Okami, Suguru; Kohtake, Naohiko

    2016-01-01

    The disease burden of malaria has decreased as malaria elimination efforts progress. The mapping approach that uses spatial risk distribution modeling needs some adjustment and reinvestigation in accordance with situational changes. Here we applied a mathematical modeling approach for standardized morbidity ratio (SMR) calculated by annual parasite incidence using routinely aggregated surveillance reports, environmental data such as remote sensing data, and non-environmental anthropogenic data to create fine-scale spatial risk distribution maps of western Cambodia. Furthermore, we incorporated a combination of containment status indicators into the model to demonstrate spatial heterogeneities of the relationship between containment status and risks. The explanatory model was fitted to estimate the SMR of each area (adjusted Pearson correlation coefficient R2 = 0.774; Akaike information criterion AIC = 149.423). A Bayesian modeling framework was applied to estimate the uncertainty of the model and cross-scale predictions. Fine-scale maps were created by the spatial interpolation of estimated SMRs at each village. Compared with geocoded case data, corresponding predicted values showed conformity [Spearman’s rank correlation r = 0.662 in the inverse distance weighed interpolation and 0.645 in ordinal kriging (95% confidence intervals of 0.414–0.827 and 0.368–0.813, respectively), Welch’s t-test; Not significant]. The proposed approach successfully explained regional malaria risks and fine-scale risk maps were created under low-to-moderate malaria transmission settings where reinvestigations of existing risk modeling approaches were needed. Moreover, different representations of simulated outcomes of containment status indicators for respective areas provided useful insights for tailored interventional planning, considering regional malaria endemicity. PMID:27415623

  18. High malaria transmission in a forested malaria focus in French Guiana: How can exophagic Anopheles darlingi thwart vector control and prevention measures?

    PubMed Central

    Vezenegho, Samuel B; Adde, Antoine; de Santi, Vincent Pommier; Issaly, Jean; Carinci, Romuald; Gaborit, Pascal; Dusfour, Isabelle; Girod, Romain; Briolant, Sébastien

    2016-01-01

    In French Guiana, malaria vector control and prevention relies on indoor residual spraying and distribution of long lasting insecticidal nets. These measures are based on solid epidemiological evidence but reveal a poor understanding of the vector. The current study investigated the behaviour of both vectors and humans in relation to the ongoing prevention strategies. In 2012 and 2013, Anopheles mosquitoes were sampled outdoors at different seasons and in various time slots. The collected mosquitoes were identified and screened for Plasmodium infection. Data on human behaviour and malaria episodes were obtained from an interview. A total of 3,135 Anopheles mosquitoes were collected, of which Anopheles darlingi was the predominant species (96.2%). For the December 2012-February 2013 period, the Plasmodium vivax infection rate for An. darlingi was 7.8%, and the entomological inoculation rate was 35.7 infective bites per person per three-month span. In spite of high bednet usage (95.7%) in 2012 and 2013, 52.2% and 37.0% of the participants, respectively, had at least one malaria episode. An. darlingi displayed heterogeneous biting behaviour that peaked between 20:30 and 22:30; however, 27.6% of the inhabitants were not yet protected by bednets by 21:30. The use of additional individual and collective protective measures is required to limit exposure to infective mosquito bites and reduce vector densities. PMID:27653361

  19. Variation in exposure to Anopheles gambiae salivary gland peptide (gSG6-P1) across different malaria transmission settings in the western Kenya highlands

    PubMed Central

    2012-01-01

    Background The existing metrics of malaria transmission are limited in sensitivity under low transmission intensity. Robust surveillance systems are needed as interventions to monitor reduced transmission and prevention of rapid reintroduction. Serological tools based on antibody responses to parasite and vector antigens are potential tools for transmission measurements. The current study sought to evaluate antibody responses to Anopheles gambiae salivary gland peptide (gSG6- P1), as a biomarker of human exposure to Anopheles bites, in different transmission settings and seasons. The comparison between anti-MSP-119 IgG immune responders and non-responders allowed exploring the robustness of the gSG6-P1 peptide as a surveillance tool in an area of decreasing malaria transmission. Methods Total IgG levels to gSG6-P1 were measured in an age-stratified cohort (< 5, 5–14 and ≥ 15 years) in a total of 1,366 participants from three localities in western Kenya [Kisii (hypoendemic), Kakamega (mesoendemic), and Kombewa (hyperendemic)] including 607 sera that were additionally tested for MSP-119 specific responses during a low and a high malaria transmission seasons. Antibody prevalence and levels were compared between localities with different transmission intensities. Regression analysis was performed to examine the association between gSG6-P1 and MSP-119 seroprevalence and parasite prevalence. Result Seroprevalence of gSG6-P1 in the uphill population was 36% while it was 50% valley bottom (χ2 = 13.2, df = 1, p < 0.001). Median gSG6-P1 antibody levels in the Valley bottom were twice as high as that observed in the uphill population [4.50 vs. 2.05, p < 0.001] and showed seasonal variation. The odds of gSG6-P1 seropositives having MSP-119 antibodies were almost three times higher than the odds of seronegatives (OR = 2.87, 95% CI [1.977, 4.176]). The observed parasite prevalence for Kisii, Kakamega and Kombewa were 4%, 19.7% and 44.6% whilst the

  20. Three-dimensional analysis of morphological changes in the malaria parasite infected red blood cell by serial block-face scanning electron microscopy.

    PubMed

    Sakaguchi, Miako; Miyazaki, Naoyuki; Fujioka, Hisashi; Kaneko, Osamu; Murata, Kazuyoshi

    2016-03-01

    The human malaria parasite, Plasmodium falciparum, exhibits morphological changes during the blood stage cycle in vertebrate hosts. Here, we used serial block-face scanning electron microscopy (SBF-SEM) to visualize the entire structures of P. falciparum-infected red blood cells (iRBCs) and to examine their morphological and volumetric changes at different stages. During developmental stages, the parasite forms Maurer's clefts and vesicles in the iRBC cytoplasm and knobs on the iRBC surface, and extensively remodels the iRBC structure for proliferation of the parasite. In our observations, the Maurer's clefts and vesicles in the P. falciparum-iRBCs, resembling the so-called tubovesicular network (TVN), were not connected to each other, and continuous membrane networks were not observed between the parasitophorous vacuole membrane (PVM) and the iRBC cytoplasmic membrane. In the volumetric analysis, the iRBC volume initially increased and then decreased to the end of the blood stage cycle. This suggests that it is necessary to absorb a substantial amount of nutrients from outside the iRBC during the initial stage, but to release waste materials from inside the iRBC at the multinucleate stage. Transportation of the materials may be through the iRBC membrane, rather than a special structure formed by the parasite, because there is no direct connection between the iRBC membrane and the parasite. These results provide new insights as to how the malaria parasite grows in the iRBC and remodels iRBC structure during developmental stages; these observation can serve as a baseline for further experiments on the effects of therapeutic agents on malaria.

  1. Longitudinal analysis of antibody responses in symptomatic malaria cases do not mirror parasite transmission in peri-urban area of Cote d’Ivoire between 2010 and 2013

    PubMed Central

    Loucoubar, Cheikh; Beourou, Sylvain; Vigan-Womas, Inès; Touré, Aissatou; Djaman, Joseph Allico

    2017-01-01

    Background In the agenda towards malaria eradication, assessment of both malaria exposure and efficacy of anti-vectorial and therapeutic strategies is a key component of management and the follow-up of field interventions. The simultaneous use of several antigens (Ags) as serological markers has the potential for accurate evaluation of malaria exposure. Here we aimed to measure the longitudinal evolution of the background levels of immunity in an urban setting in confirmed clinical cases of malaria. Methods A retrospective serological cross-sectional study on was carried out using 234 samples taken from 2010 to 2013 in peri-urban sentinel facility of Cote d’Ivoire. Antibody responses to recombinant proteins or BSA-peptides, 8 Plasmodium falciparum (PfAMA1, PfMSP4, PfMSP1, PfEMP1-DBL1α1-PF13, PfLSA1-41, PfLSA3-NR2, PfGLURP and PfCSP), one P. malariae (PmCSP) and one Anopheles gambiae salivary (gSG6-P1) antigens were measured using magnetic bead-based multiplex immunoassay (MBA). Total anti- P. falciparum IgG responses against schizont lysate from african 07/03 strain (adapted to culture) and 3D7 strain was measured by ELISA. Results High prevalence (7–93%) and levels of antibody responses to most of the antigens were evidenced. However, analysis showed only marginal decreasing trend of Ab responses from 2010 to 2013 that did not parallel the reduction of clinical malaria prevalence following the implementation of intervention in this area. There was a significant inverse correlation between Ab responses and parasitaemia (P<10−3, rho = 0.3). The particular recruitment of asymptomatic individuals in 2011 underlined a high background level of immunity almost equivalent to symptomatic patients, possibly obscuring observable yearly variations. Conclusion The use of cross-sectional clinical malaria surveys and MBA can help to identify endemic sites where control measures have unequal impact providing relevant information about population immunity and possible

  2. The Nonartemisinin Sesquiterpene Lactones Parthenin and Parthenolide Block Plasmodium falciparum Sexual Stage Transmission

    PubMed Central

    Balaich, Jared N.; Mathias, Derrick K.; Torto, Baldwyn; Jackson, Bryan T.; Tao, Dingyin; Ebrahimi, Babak; Tarimo, Brian B.; Cheseto, Xavier; Foster, Woodbridge A.

    2016-01-01

    Parthenin and parthenolide are natural products that are closely related in structure to artemisinin, which is also a sesquiterpene lactone (SQL) and one of the most important antimalarial drugs available. Parthenin, like artemisinin, has an effect on Plasmodium blood stage development. We extended the evaluation of parthenin as a potential therapeutic for the transmissible stages of Plasmodium falciparum as it transitions between human and mosquito, with the aim of gaining potential mechanistic insight into the inhibitory activity of this compound. We posited that if parthenin targets different biological pathways in the parasite, this in turn could pave the way for the development of druggable compounds that could prevent the spread of artemisinin-resistant parasites. We examined parthenin's effect on male gamete activation and the ookinete-to-oocyst transition in the mosquito as well as on stage V gametocytes that are present in peripheral blood. Parthenin arrested parasite development for each of the stages tested. The broad inhibitory properties of parthenin on the evaluated parasite stages may suggest different mechanisms of action between parthenin and artemisinin. Parthenin's cytotoxicity notwithstanding, its demonstrated activity in this study suggests that structurally related SQLs with a better safety profile deserve further exploration. We used our battery of assays to test parthenolide, which has a more compelling safety profile. Parthenolide demonstrated activity nearly identical to that of parthenin against P. falciparum, highlighting its potential as a possible transmission-blocking drug scaffold. We discuss the context of the evidence with respect to the next steps toward expanding the current antimalarial arsenal. PMID:26787692

  3. The Nonartemisinin Sesquiterpene Lactones Parthenin and Parthenolide Block Plasmodium falciparum Sexual Stage Transmission.

    PubMed

    Balaich, Jared N; Mathias, Derrick K; Torto, Baldwyn; Jackson, Bryan T; Tao, Dingyin; Ebrahimi, Babak; Tarimo, Brian B; Cheseto, Xavier; Foster, Woodbridge A; Dinglasan, Rhoel R

    2016-04-01

    Parthenin and parthenolide are natural products that are closely related in structure to artemisinin, which is also a sesquiterpene lactone (SQL) and one of the most important antimalarial drugs available. Parthenin, like artemisinin, has an effect onPlasmodiumblood stage development. We extended the evaluation of parthenin as a potential therapeutic for the transmissible stages ofPlasmodium falciparumas it transitions between human and mosquito, with the aim of gaining potential mechanistic insight into the inhibitory activity of this compound. We posited that if parthenin targets different biological pathways in the parasite, this in turn could pave the way for the development of druggable compounds that could prevent the spread of artemisinin-resistant parasites. We examined parthenin's effect on male gamete activation and the ookinete-to-oocyst transition in the mosquito as well as on stage V gametocytes that are present in peripheral blood. Parthenin arrested parasite development for each of the stages tested. The broad inhibitory properties of parthenin on the evaluated parasite stages may suggest different mechanisms of action between parthenin and artemisinin. Parthenin's cytotoxicity notwithstanding, its demonstrated activity in this study suggests that structurally related SQLs with a better safety profile deserve further exploration. We used our battery of assays to test parthenolide, which has a more compelling safety profile. Parthenolide demonstrated activity nearly identical to that of parthenin againstP. falciparum, highlighting its potential as a possible transmission-blocking drug scaffold. We discuss the context of the evidence with respect to the next steps toward expanding the current antimalarial arsenal.

  4. Effects of information transmission delay and channel blocking on synchronization in scale-free Hodgkin-Huxley neuronal networks

    NASA Astrophysics Data System (ADS)

    Wang, Qing-Yun; Zheng, Yan-Hong

    2011-12-01

    In this paper, we investigate the evolution of spatiotemporal patterns and synchronization transitions in dependence on the information transmission delay and ion channel blocking in scale-free neuronal networks. As the underlying model of neuronal dynamics, we use the Hodgkin-Huxley equations incorporating channel blocking and intrinsic noise. It is shown that delays play a significant yet subtle role in shaping the dynamics of neuronal networks. In particular, regions of irregular and regular propagating excitatory fronts related to the synchronization transitions appear intermittently as the delay increases. Moreover, the fraction of working sodium and potassium ion channels can also have a significant impact on the spatiotemporal dynamics of neuronal networks. As the fraction of blocked sodium channels increases, the frequency of excitatory events decreases, which in turn manifests as an increase in the neuronal synchrony that, however, is dysfunctional due to the virtual absence of large-amplitude excitations. Expectedly, we also show that larger coupling strengths improve synchronization irrespective of the information transmission delay and channel blocking. The presented results are also robust against the variation of the network size, thus providing insights that could facilitate understanding of the joint impact of ion channel blocking and information transmission delay on the spatiotemporal dynamics of neuronal networks.

  5. A small mitochondrial protein present in myzozoans is essential for malaria transmission

    PubMed Central

    Klug, Dennis; Mair, Gunnar R.; Frischknecht, Friedrich; Douglas, Ross G.

    2016-01-01

    Myzozoans (which include dinoflagellates, chromerids and apicomplexans) display notable divergence from their ciliate sister group, including a reduced mitochondrial genome and divergent metabolic processes. The factors contributing to these divergent processes are still poorly understood and could serve as potential drug targets in disease-causing protists. Here, we report the identification and characterization of a small mitochondrial protein from the rodent-infecting apicomplexan parasite Plasmodium berghei that is essential for development in its mosquito host. Parasites lacking the gene mitochondrial protein ookinete developmental defect (mpodd) showed malformed parasites that were unable to transmit to mosquitoes. Knockout parasites displayed reduced mitochondrial mass without affecting organelle integrity, indicating no role of the protein in mitochondrial biogenesis or morphology maintenance but a likely role in mitochondrial import or metabolism. Using genetic complementation experiments, we identified a previously unrecognized Plasmodium falciparum homologue that can rescue the mpodd(−) phenotype, thereby showing that the gene is functionally conserved. As far as can be detected, mpodd is found in myzozoans, has homologues in the phylum Apicomplexa and appears to have arisen in free-living dinoflagellates. This suggests that the MPODD protein has a conserved mitochondrial role that is important for myzozoans. While previous studies identified a number of essential proteins which are generally highly conserved evolutionarily, our study identifies, for the first time, a non-canonical protein fulfilling a crucial function in the mitochondrion during parasite transmission. PMID:27053680

  6. Transmission-blocking antibodies against mosquito C-type lectins for dengue prevention.

    PubMed

    Liu, Yang; Zhang, Fuchun; Liu, Jianying; Xiao, Xiaoping; Zhang, Siyin; Qin, Chengfeng; Xiang, Ye; Wang, Penghua; Cheng, Gong

    2014-02-01

    C-type lectins are a family of proteins with carbohydrate-binding activity. Several C-type lectins in mammals or arthropods are employed as receptors or attachment factors to facilitate flavivirus invasion. We previously identified a C-type lectin in Aedes aegypti, designated as mosquito galactose specific C-type lectin-1 (mosGCTL-1), facilitating the attachment of West Nile virus (WNV) on the cell membrane. Here, we first identified that 9 A. aegypti mosGCTL genes were key susceptibility factors facilitating DENV-2 infection, of which mosGCTL-3 exhibited the most significant effect. We found that mosGCTL-3 was induced in mosquito tissues with DENV-2 infection, and that the protein interacted with DENV-2 surface envelop (E) protein and virions in vitro and in vivo. In addition, the other identified mosGCTLs interacted with the DENV-2 E protein, indicating that DENV may employ multiple mosGCTLs as ligands to promote the infection of vectors. The vectorial susceptibility factors that facilitate pathogen invasion may potentially be explored as a target to disrupt the acquisition of microbes from the vertebrate host. Indeed, membrane blood feeding of antisera against mosGCTLs dramatically reduced mosquito infective ratio. Hence, the immunization against mosGCTLs is a feasible approach for preventing dengue infection. Our study provides a future avenue for developing a transmission-blocking vaccine that interrupts the life cycle of dengue virus and reduces disease burden.

  7. A progressive transmission image coder using linear phase uniform filterbanks as block transforms.

    PubMed

    Tran, T D; Nguyen, T Q

    1999-01-01

    This paper presents a novel image coding scheme using M-channel linear phase perfect reconstruction filterbanks (LPPRFBs) in the embedded zerotree wavelet (EZW) framework introduced by Shapiro (1993). The innovation here is to replace the EZWs dyadic wavelet transform by M-channel uniform-band maximally decimated LPPRFBs, which offer finer frequency spectrum partitioning and higher energy compaction. The transform stage can now be implemented as a block transform which supports parallel processing and facilitates region-of-interest coding/decoding. For hardware implementation, the transform boasts efficient lattice structures, which employ a minimal number of delay elements and are robust under the quantization of lattice coefficients. The resulting compression algorithm also retains all the attractive properties of the EZW coder and its variations such as progressive image transmission, embedded quantization, exact bit rate control, and idempotency. Despite its simplicity, our new coder outperforms some of the best image coders published previously in the literature, for almost all test images (especially natural, hard-to-code ones) at almost all bit rates.

  8. Behavioral heterogeneity of Anopheles darlingi (Diptera: Culicidae) and malaria transmission dynamics along the Maroni River, Suriname, French Guiana.

    PubMed

    Hiwat, H; Issaly, J; Gaborit, P; Somai, A; Samjhawan, A; Sardjoe, P; Soekhoe, T; Girod, R

    2010-03-01

    The border area between Suriname and French Guiana is considered the most affected malaria area in South America. A one-year cooperative malaria vector study was performed by the two countries, between March 2004 and February 2005, in four villages. Anopheles darlingi proved to be the most abundant anopheline species. Human biting rates differed between villages. The differential effect of high rainfall on mosquito densities in the villages suggests variation in breeding sites. Overall parity rates were low, with means varying from 0.31 to 0.56 per study site. Of the 2045 A. darlingi mosquitoes collected, 13 were found to be infected with Plasmodium: ten P. falciparum, two P. malariae and one mixed P. malariae/P. vivax. The overall annual entomological inoculation rates in the villages ranged from 8.7 to 66.4. There was an apparent lack of relationship between number of malaria cases and periods of high mosquito density. The tendency of Anopheles darlingi to bite during sleeping hours provides opportunity for malaria control using impregnated bed nets, a strategy just introduced in Suriname that may also find its way into French Guiana.

  9. Cost-effectiveness analysis of three health interventions to prevent malaria in pregnancy in an area of low transmission in Uganda

    PubMed Central

    Hansen, Kristian Schultz; Ndyomugyenyi, Richard; Magnussen, Pascal; Clarke, Siân E

    2014-01-01

    Pregnant women and their unborn children are vulnerable to malaria increasing the risk of maternal anaemia, low birth weight (LBW) and intrauterine growth retardation. There is little evidence on the cost-effectiveness of intermittent preventive treatment in pregnancy (IPTp) and insecticide-treated bed nets (ITNs) in areas of low transmission. A randomised controlled trial with three arms was conducted in antenatal clinics in Kabale District, Uganda, an epidemic-prone highland area of low malaria transmission. The interventions were (i) IPTp with sulphadoxine/pyrimethamine (SP) given twice during pregnancy (IPTp-SP); (ii) ITNs alone; and (iii) a combined intervention with both ITNs and IPTp-SP. Primary health outcomes were LBW and maternal anaemia. The costs of providing IPTp-SP and ITNs as well as treatment of malaria episodes were captured from all health centres in the study area. There were no significant differences in health outcomes among the three interventions. The cost-effectiveness analysis and sensitivity analyses performed did not provide convincing support for replacing IPTp-SP (current policy) by ITNs alone or by a combined intervention in this low transmission setting on economic grounds. The cost per pregnant woman of providing the services was lowest for the IPTp-SP intervention (US$0.79 per woman) followed by ITNs (US$1.71) and the combined intervention of IPTp-SP + ITNs (US$2.48). The relative cost-effectiveness of antenatal distribution of ITNs might improve if the cost savings accruing from continued use of a long-lasting insecticidal net after pregnancy as well as positive externalities were also taken into account, and this warrants further study. PMID:24030879

  10. Impact of promoting longer-lasting insecticide treatment of bed nets upon malaria transmission in a rural Tanzanian setting with pre-existing high coverage of untreated nets

    PubMed Central

    2010-01-01

    Background The communities of Namawala and Idete villages in southern Tanzania experienced extremely high malaria transmission in the 1990s. By 2001-03, following high usage rates (75% of all age groups) of untreated bed nets, a 4.2-fold reduction in malaria transmission intensity was achieved. Since 2006, a national-scale programme has promoted the use of longer-lasting insecticide treatment kits (consisting of an insecticide plus binder) co-packaged with all bed nets manufactured in the country. Methods The entomological inoculation rate (EIR) was estimated through monthly surveys in 72 houses randomly selected in each of the two villages. Mosquitoes were caught using CDC light traps placed beside occupied bed nets between January and December 2008 (n = 1,648 trap nights). Sub-samples of mosquitoes were taken from each trap to determine parity status, sporozoite infection and Anopheles gambiae complex sibling species identity. Results Compared with a historical mean EIR of ~1400 infectious bites/person/year (ib/p/y) in 1990-94; the 2008 estimate of 81 ib/p/y represents an 18-fold reduction for an unprotected person without a net. The combined impact of longer-lasting insecticide treatments as well as high bed net coverage was associated with a 4.6-fold reduction in EIR, on top of the impact from the use of untreated nets alone. The scale-up of bed nets and subsequent insecticidal treatment has reduced the density of the anthropophagic, endophagic primary vector species, Anopheles gambiae sensu stricto, by 79%. In contrast, the reduction in density of the zoophagic, exophagic sibling species Anopheles arabiensis was only 38%. Conclusion Insecticide treatment of nets reduced the intensity of malaria transmission in addition to that achieved by the untreated nets alone. Impacts were most pronounced against the highly anthropophagic, endophagic primary vector, leading to a shift in the sibling species composition of the A. gambiae complex. PMID:20579399

  11. Host matrix metalloproteinases in cerebral malaria: new kids on the block against blood–brain barrier integrity?

    PubMed Central

    2014-01-01

    Cerebral malaria (CM) is a life-threatening complication of falciparum malaria, associated with high mortality rates, as well as neurological impairment in surviving patients. Despite disease severity, the etiology of CM remains elusive. Interestingly, although the Plasmodium parasite is sequestered in cerebral microvessels, it does not enter the brain parenchyma: so how does Plasmodium induce neuronal dysfunction? Several independent research groups have suggested a mechanism in which increased blood–brain barrier (BBB) permeability might allow toxic molecules from the parasite or the host to enter the brain. However, the reported severity of BBB damage in CM is variable depending on the model system, ranging from mild impairment to full BBB breakdown. Moreover, the factors responsible for increased BBB permeability are still unknown. Here we review the prevailing theories on CM pathophysiology and discuss new evidence from animal and human CM models implicating BBB damage. Finally, we will review the newly-described role of matrix metalloproteinases (MMPs) and BBB integrity. MMPs comprise a family of proteolytic enzymes involved in modulating inflammatory response, disrupting tight junctions, and degrading sub-endothelial basal lamina. As such, MMPs represent potential innovative drug targets for CM. PMID:24467887

  12. Individual and Household Level Risk Factors Associated with Malaria in Nchelenge District, a Region with Perennial Transmission: A Serial Cross-Sectional Study from 2012 to 2015

    PubMed Central

    Pinchoff, Jessie; Chaponda, Mike; Shields, Timothy M.; Sichivula, James; Muleba, Mbanga; Mulenga, Modest; Kobayashi, Tamaki; Curriero, Frank C.; Moss, William J.

    2016-01-01

    Background The scale-up of malaria control interventions has resulted in substantial declines in transmission in some but not all regions of sub-Saharan Africa. Understanding factors associated with persistent malaria transmission despite control efforts may guide targeted interventions to high-risk areas and populations. Methods Household malaria surveys were conducted in Nchelenge District, Luapula Province, in northern Zambia. Structures that appeared to be households were enumerated from a high-resolution satellite image and randomly sampled for enrollment. Households were enrolled into cross-sectional (single visit) or longitudinal (visits every other month) cohorts but analyses were restricted to cross-sectional visits and the first visit to longitudinal households. During study visits, a questionnaire was administered to adults and caretakers of children and a blood sample was collected for a malaria rapid diagnostic test (RDT) from all household residents. Characteristics associated with RDT positivity were analyzed using multi-level models. Results A total of 2,486 individuals residing within 742 households were enrolled between April 2012 and July 2015. Over this period, 51% of participants were RDT positive. Forty-three percent of all RDT positive individuals were between the ages of 5 and 17 years although this age group comprised only 30% of study participants. In a multivariable model, the odds being RDT positive were highest in 5–17 year olds and did not vary by season. Children 5–17 years of age had 8.83 higher odds of being RDT positive compared with those >18 years of age (95% CI: 6.13, 12.71); there was an interaction between age and report of symptoms, with an almost 50% increased odds of report of symptoms with decreasing age category (OR = 1.49; 95% CI 1.11, 2.00). Conclusions Children and adolescents between the ages of 5 and 17 were at the highest risk of malaria infection throughout the year. School-based programs may be effective at

  13. Blocking HIV-1 transmission in the female reproductive tract: from microbicide development to exploring local antiviral responses

    PubMed Central

    Eid, Sahar G; Mangan, Niamh E; Hertzog, Paul J; Mak, Johnson

    2015-01-01

    The majority of new HIV-1 infections are transmitted sexually by penetrating the mucosal barrier to infect target cells. The development of microbicides to restrain heterosexual HIV-1 transmission in the past two decades has proven to be a challenging endeavor. Therefore, better understanding of the tissue environment in the female reproductive tract may assist in the development of the next generation of microbicides to prevent HIV-1 transmission. In this review, we highlight the important factors involved in the heterosexual transmission of HIV-1, provide an update on microbicides' clinical trials, and discuss how different delivery platforms and local immunity may empower the development of next generation of microbicide to block HIV-1 transmission in the female reproductive tract. PMID:26682051

  14. A qualitative study on caretakers' perceived need of bed-nets after reduced malaria transmission in Zanzibar, Tanzania

    PubMed Central

    2012-01-01

    Background The elimination of malaria in Zanzibar is highly dependent on sustained effective coverage of bed-nets to avoid malaria resurgence. The Health Belief Model (HBM) framework was used to explore the perceptions of malaria and bed-net use after a noticeable reduction in malaria incidence. Methods Nineteen in-depth interviews were conducted with female and male caretakers of children under five in North A district, Zanzibar. Deductive content analysis was used to identify meaning units that were condensed, coded and assigned to pre-determined elements of the HBM. Results Awareness of malaria among caretakers was high but the illness was now seen as easily curable and uncommon. In addition to the perceived advantage of providing protection against malaria, bed-nets were also thought to be useful for avoiding mosquito nuisance, especially during the rainy season when the malaria and mosquito burden is high. The discomfort of sleeping under a net during the hot season was the main barrier that interrupted consistent bed-net usage. The main cue to using a bed-net was high mosquito density, and children were prioritized when it came to bed-net usage. Caretakers had high perceived self-efficacy and did not find it difficult to use bed-nets. Indoor Residual Spraying (IRS), which was recognized as an additional means of mosquito prevention, was not identified as an alternative for bed-nets. A barrier to net ownership was the increasingly high cost of bed-nets. Conclusions Despite the reduction in malaria incidence and the resulting low malaria risk perceptions among caretakers, the benefit of bed-nets as the most proficient protection against mosquito bites upholds their use. This, in combination with the perceived high self-efficacy of caretakers, supports bed-net usage, while seasonality interrupts consistent use. High effective coverage of bed-nets could be further improved by reinforcing the benefits of bed-nets, addressing the seasonal heat barrier by using nets

  15. Infection dynamics of endemic malaria in a wild bird population: parasite species-dependent drivers of spatial and temporal variation in transmission rates.

    PubMed

    Lachish, Shelly; Knowles, Sarah C L; Alves, Ricardo; Wood, Matthew J; Sheldon, Ben C

    2011-11-01

    1. Investigating the ecological context in which host-parasite interactions occur and the roles of biotic and abiotic factors in forcing infection dynamics is essential to understanding disease transmission, spread and maintenance. 2. Despite their prominence as model host-pathogen systems, the relative influence of environmental heterogeneity and host characteristics in influencing the infection dynamics of avian blood parasites has rarely been assessed in the wild, particularly at a within-population scale. 3. We used a novel multievent modelling framework (an extension of multistate mark-recapture modelling) that allows for uncertainty in disease state, to estimate transmission parameters and assess variation in the infection dynamics of avian malaria in a large, longitudinally sampled data set of breeding blue tits infected with two divergent species of Plasmodium parasites. 4. We found striking temporal and spatial heterogeneity in the disease incidence rate and the likelihood of recovery within this single population and demonstrate marked differences in the relative influence of environmental and host factors in forcing the infection dynamics of the two Plasmodium species. 5. Proximity to a permanent water source greatly influenced the transmission rates of P. circumflexum, but not of P. relictum, suggesting that these parasites are transmitted by different vectors. 6. Host characteristics (age/sex) were found to influence infection rates but not recovery rates, and their influence on infection rates was also dependent on parasite species: P. relictum infection rates varied with host age, whilst P. circumflexum infection rates varied with host sex. 7. Our analyses reveal that transmission of endemic avian malaria is a result of complex interactions between biotic and abiotic components that can operate on small spatial scales and demonstrate that knowledge of the drivers of spatial and temporal heterogeneity in disease transmission will be

  16. [Identification of anopheles breeding sites in the residual foci of low malaria transmission «hotspots» in Central and Western Senegal].

    PubMed

    Sy, O; Konaté, L; Ndiaye, A; Dia, I; Diallo, A; Taïrou, F; Bâ, E L; Gomis, J F; Ndiaye, J L; Cissé, B; Gaye, O; Faye, O

    2016-02-01

    Malaria incidence has markedly declined in the Mbour, Fatick, Niakhar and Bambey districts (central and western Senegal) thanks to a scaling up of effective control measures namely LLINs (Long Lasting Insecticide Treated Net), ACTs (Artesunate Combination Therapy) and promoting care seeking. However malaria cases are now maintained by foci of transmission called hotspots. We evaluate the role of anopheles breeding sites in the identification of malaria hotspots in the health districts of Mbour, Fatick, Niakhar and Bambey. Surveys of breeding sites were made in 6 hotspot villages and 4 non-hotspot villages. A sample was taken in each water point with mosquito larvae by dipping method and the collected specimens were identified to the genus level. Additional parameters as name of the village and breeding sites, type of collection, original water turbidity, presence of vegetation, proximity to dwellings, geographic coordinates, sizes were also collected. Sixty-two water collections were surveyed and monitored between 2013 and 2014. Temporary natural breeding sites were predominant regardless of the epidemiological status of the village. Among the 31 breeding sites located within 500 meters of dwellings in hotspots villages, 70% carried Anopheles larvae during the rainy season while 43% of the 21 breeding sites located at similar distances in non-hotspot villages carried Anopheles larvae during the same period (P = 0.042). At the end of the rainy season, the trend is the same with 27% of positive breeding sites in hotspots and 14% in non-hotspots villages. The breeding sites encountered in hotspots villages are mostly small to medium size and are more productive by Anopheles larvae than those found in non-hotspot area. This study showed that the high frequency of smallest and productive breeding sites around and inside the villages can create conditions of residual transmission.

  17. On the use of satellite-based estimates of rainfall temporal distribution to simulate the potential for malaria transmission in rural Africa

    NASA Astrophysics Data System (ADS)

    Yamana, Teresa K.; Eltahir, Elfatih A. B.

    2011-02-01

    This paper describes the use of satellite-based estimates of rainfall to force the Hydrology, Entomology and Malaria Transmission Simulator (HYDREMATS), a hydrology-based mechanistic model of malaria transmission. We first examined the temporal resolution of rainfall input required by HYDREMATS. Simulations conducted over Banizoumbou village in Niger showed that for reasonably accurate simulation of mosquito populations, the model requires rainfall data with at least 1 h resolution. We then investigated whether HYDREMATS could be effectively forced by satellite-based estimates of rainfall instead of ground-based observations. The Climate Prediction Center morphing technique (CMORPH) precipitation estimates distributed by the National Oceanic and Atmospheric Administration are available at a 30 min temporal resolution and 8 km spatial resolution. We compared mosquito populations simulated by HYDREMATS when the model is forced by adjusted CMORPH estimates and by ground observations. The results demonstrate that adjusted rainfall estimates from satellites can be used with a mechanistic model to accurately simulate the dynamics of mosquito populations.

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

    PubMed Central

    Sinden, Robert E.; Poulton, Ian D.; Griffin, Jamie T.; Upton, Leanna M.; Sala, Katarzyna A.; Angrisano, Fiona; Hill, Adrian V. S.; Blagborough, Andrew M.

    2017-01-01

    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. PMID:28081253

  19. Evolution of the Transmission-Blocking Vaccine Candidates Pvs28 and Pvs25 in Plasmodium vivax: Geographic Differentiation and Evidence of Positive Selection

    PubMed Central

    Cornejo, Omar E.; Durrego, Ester; Stanley, Craig E.; Castillo, Andreína I.; Herrera, Sócrates; Escalante, Ananias A.

    2016-01-01

    Transmission-blocking (TB) vaccines are considered an important tool for malaria control and elimination. Among all the antigens characterized as TB vaccines against Plasmodium vivax, the ookinete surface proteins Pvs28 and Pvs25 are leading candidates. These proteins likely originated by a gene duplication event that took place before the radiation of the known Plasmodium species to primates. We report an evolutionary genetic analysis of a worldwide sample of pvs28 and pvs25 alleles. Our results show that both genes display low levels of genetic polymorphism when compared to the merozoite surface antigens AMA-1 and MSP-1; however, both ookinete antigens can be as polymorphic as other merozoite antigens such as MSP-8 and MSP-10. We found that parasite populations in Asia and the Americas are geographically differentiated with comparable levels of genetic diversity and specific amino acid replacements found only in the Americas. Furthermore, the observed variation was mainly accumulated in the EGF2- and EGF3-like domains for P. vivax in both proteins. This pattern was shared by other closely related non-human primate parasites such as Plasmodium cynomolgi, suggesting that it could be functionally important. In addition, examination with a suite of evolutionary genetic analyses indicated that the observed patterns are consistent with positive natural selection acting on Pvs28 and Pvs25 polymorphisms. The geographic pattern of genetic differentiation and the evidence for positive selection strongly suggest that the functional consequences of the observed polymorphism should be evaluated during development of TBVs that include Pvs25 and Pvs28. PMID:27347876

  20. Mixture block coding with progressive transmission in packet video. Appendix 1: Item 2. M.S. Thesis

    NASA Technical Reports Server (NTRS)

    Chen, Yun-Chung

    1989-01-01

    Video transmission will become an important part of future multimedia communication because of dramatically increasing user demand for video, and rapid evolution of coding algorithm and VLSI technology. Video transmission will be part of the broadband-integrated services digital network (B-ISDN). Asynchronous transfer mode (ATM) is a viable candidate for implementation of B-ISDN due to its inherent flexibility, service independency, and high performance. According to the characteristics of ATM, the information has to be coded into discrete cells which travel independently in the packet switching network. A practical realization of an ATM video codec called Mixture Block Coding with Progressive Transmission (MBCPT) is presented. This variable bit rate coding algorithm shows how a constant quality performance can be obtained according to user demand. Interactions between codec and network are emphasized including packetization, service synchronization, flow control, and error recovery. Finally, some simulation results based on MBCPT coding with error recovery are presented.

  1. [Vectorial transmission of malaria in a village along the Niger River and its fishing hamlet (Kéniéroba and Fourda, Mali)].

    PubMed

    Keïta, M; Baber, I; Sogoba, N; Maïga, H M; Diallo, M'b; Doumbia, S; Traoré, S F

    2014-12-01

    A better understanding of malaria transmission dynamics is an essential element in the development of any targeted vector control strategy. The objective of this study was to better understand malaria transmission dynamics along the Niger River in Sudan savanna zone of Mali. Trough cross-sectional surveys, Anopheline larvae were collected by WHO standard dipping technique, and vector adults by Human Landing and pyrethrum spray catches methods. The vector population was composed of An. gambiae s.l. (> 99%) and An. funestus (< 1%). An. gambiae s.l. was composed of 96% and 98% of An. gambiae s.s. respectively in Kéniéroba and Fourda. An. gambiae s.s. was in majority composed of its molecular form M in both locations. The density of An. gambiae s.l was higher in the dry season in the immediate vicinity of the river (fishing hamlet Fourda) compared to farther inland Kéniéroba. The average infection rate of An. gambiae s.l. was 3.63% and 4.06% in Kéniéroba and Fourda respectively. The average entomological inoculation rate (EIR) during the study period was almost similar in Kéniéroba (0.70 infective bites/person/month) and Fourda (0.69 infective bites/person/month). The means EIRs over each of the rainy season 2006 and 2007 were always higher than the one of the dry season 2007 in both localities, with much smaller amplitude in Fourda than in Kéniéroba. However, the level of the transmission was 2.31 (0.37/0.16) times higher in Fourda than in Kéniéroba during the dry season.We conclude that in Sudan savanna zone of Mali, malaria transmission along the river is continuous throughout the year, but it is more intense in the immediate vicinity of the river during the dry season than during the rainy season in opposition to more distant localities to the river and vector control should not be focused only on the rainy in such setting.

  2. Behavioral patterns, parity rate and natural infection analysis in anopheline species involved in the transmission of malaria in the northeastern Brazilian Amazon region.

    PubMed

    Barbosa, Ledayane Mayana Costa; Souto, Raimundo Nonato Picanço; Dos Anjos Ferreira, Ricardo Marcelo; Scarpassa, Vera Margarete

    2016-12-01

    The characterization of behavioral patterns allows a better understanding of the transmission dynamics and the design of more effective malaria vector control strategies. This study analyzed the behavioral patterns of the Anopheles species of the Coração district situated in the northeast of the Brazilian Amazon region. The behavioral patterns of the anopheline species were measured based on the 36 collection sites of this district from December 2010 to November 2011. Collections of four hours for three consecutive nights each month and four 12-h collections, comprising two in the rainy season and two in the dry season, were performed. Furthermore, to infer the anthropophily and zoophily indexes, four additional four-hour collections were performed. The samples were also evaluated for parity rate and natural infectivity for Plasmodium spp. A total of 1689 anophelines were captured, comprising of nine species and two subgenera (Nyssorhynchus - six species, and Anopheles - three species). Anopheles darlingi was the most abundant and widely distributed species in the area, followed by A. braziliensis and A.marajoara. Anopheles darlingi and A. marajoara were the only species present in the four collections of 12-h, but only A. darlingi showed activity throughout night. Anopheles darlingi was the most anthropophilic species (AI=0.40), but the zoophily index was higher (ZI=0.60), revealing an eclectic and opportunistic behavior. Of the six most frequent species, A. nuneztovari s.l. was the most zoophilic species (ZI=1.00). All captured species showed predominance towards biting in outdoor environments. Anopheles darlingi and A. braziliensis showed multimodal biting peaks, whereas A. marajoara revealed a stable pattern, with the biting peak after sunset. Using the PCR technique, no anopheline was found infected with the malaria parasite. Since A. darlingi and A. marajoara are recognized as important vectors in this region, the district of Coração may be considered as

  3. Abasic Phosphorothioate Oligomers Inhibit HIV-1 Reverse Transcription and Block Virus Transmission across Polarized Ectocervical Organ Cultures

    PubMed Central

    Fraietta, Joseph A.; Mueller, Yvonne M.; Lozenski, Karissa L.; Ratner, Deena; Boesteanu, Alina C.; Hancock, Aidan S.; Lackman-Smith, Carol; Zentner, Isaac J.; Chaiken, Irwin M.; Chung, Suhman; LeGrice, Stuart F. J.; Snyder, Beth A.; Mankowski, Marie K.; Jones, Natalie M.; Hope, Jennifer L.; Gupta, Phalguni; Anderson, Sharon H.; Wigdahl, Brian

    2014-01-01

    In the absence of universally available antiretroviral (ARV) drugs or a vaccine against HIV-1, microbicides may offer the most immediate hope for controlling the AIDS pandemic. The most advanced and clinically effective microbicides are based on ARV agents that interfere with the earliest stages of HIV-1 replication. Our objective was to identify and characterize novel ARV-like inhibitors, as well as demonstrate their efficacy at blocking HIV-1 transmission. Abasic phosphorothioate 2′ deoxyribose backbone (PDB) oligomers were evaluated in a variety of mechanistic assays and for their ability to inhibit HIV-1 infection and virus transmission through primary human cervical mucosa. Cellular and biochemical assays were used to elucidate the antiviral mechanisms of action of PDB oligomers against both lab-adapted and primary CCR5- and CXCR4-utilizing HIV-1 strains, including a multidrug-resistant isolate. A polarized cervical organ culture was used to test the ability of PDB compounds to block HIV-1 transmission to primary immune cell populations across ectocervical tissue. The antiviral activity and mechanisms of action of PDB-based compounds were dependent on oligomer size, with smaller molecules preventing reverse transcription and larger oligomers blocking viral entry. Importantly, irrespective of molecular size, PDBs potently inhibited virus infection and transmission within genital tissue samples. Furthermore, the PDB inhibitors exhibited excellent toxicity and stability profiles and were found to be safe for vaginal application in vivo. These results, coupled with the previously reported intrinsic anti-inflammatory properties of PDBs, support further investigations in the development of PDB-based topical microbicides for preventing the global spread of HIV-1. PMID:25224013

  4. Effects of transmission-blocking immunity on Plasmodium vivax infections in Anopheles albimanus populations.

    PubMed

    Ramsey, J M; Salinas, E; Rodriguez, M H; Beaudoin, R L

    1994-02-01

    Two colonized populations of Anopheles albimanus isolated from the Suchiate region, Chiapas State, Mexico, were compared for their susceptibility to coindigenous Plasmodium vivax. Groups of mosquitoes were fed in vitro with either autologous donor blood or the same blood cells substituted with serum negative for anti-gametocyte antibody. Significant differences in susceptibility between the 2 colonies were encountered if the autologous blood from a patient was fed to mosquitoes: mean infection rates of AnA2-positive groups was double that in AnA1 mosquitoes. Consistent for both colonies, only 23.6% of samples positive from malaria-negative serum-substituted blood were infected with an autologous blood feed. Vector competence in these mosquito populations was partially linked to the human populations's immune response to the parasite.

  5. Malaria Facts

    MedlinePlus

    ... Laveran and the Discovery of the Malaria Parasite Ross and the Discovery that Mosquitoes Transmit Malaria Parasites ... for work associated with malaria: to Sir Ronald Ross (1902), Charles Louis Alphonse Laveran (1907), Julius Wagner- ...

  6. Determinants of the accuracy of rapid diagnostic tests in malaria case management: evidence from low and moderate transmission settings in the East African highlands

    PubMed Central

    Abeku, Tarekegn A; Kristan, Mojca; Jones, Caroline; Beard, James; Mueller, Dirk H; Okia, Michael; Rapuoda, Beth; Greenwood, Brian; Cox, Jonathan

    2008-01-01

    Background The accuracy of malaria diagnosis has received renewed interest in recent years due to changes in treatment policies in favour of relatively high-cost artemisinin-based combination therapies. The use of rapid diagnostic tests (RDTs) based on histidine-rich protein 2 (HRP2) synthesized by Plasmodium falciparum has been widely advocated to save costs and to minimize inappropriate treatment of non-malarial febrile illnesses. HRP2-based RDTs are highly sensitive and stable; however, their specificity is a cause for concern, particularly in areas of intense malaria transmission due to persistence of HRP2 antigens from previous infections. Methods In this study, 78,454 clinically diagnosed malaria patients were tested using HRP2-based RDTs over a period of approximately four years in four highland sites in Kenya and Uganda representing hypoendemic to mesoendemic settings. In addition, the utility of the tests was evaluated in comparison with expert microscopy for disease management in 2,241 subjects in two sites with different endemicity levels over four months. Results RDT positivity rates varied by season and year, indicating temporal changes in accuracy of clinical diagnosis. Compared to expert microscopy, the sensitivity, specificity, positive predictive value and negative predictive value of the RDTs in a hypoendemic site were 90.0%, 99.9%, 90.0% and 99.9%, respectively. Corresponding measures at a mesoendemic site were 91.0%, 65.0%, 71.6% and 88.1%. Although sensitivities at the two sites were broadly comparable, levels of specificity varied considerably between the sites as well as according to month of test, age of patient, and presence or absence of fever during consultation. Specificity was relatively high in older age groups and increased towards the end of the transmission season, indicating the role played by anti-HRP2 antibodies. Patients with high parasite densities were more likely to test positive with RDTs than those with low density

  7. Effect of conduction block at axon bifurcations on synaptic transmission to different postsynaptic neurones in the leech.

    PubMed Central

    Gu, X N

    1991-01-01

    1. The cutaneous receptive field of the medial pressure (mP) sensory neurone in the leech has been examined. The cell has one major receptive field and an anterior and a posterior minor receptive field, principally on lateral and dorsal skin. The two minor receptive fields are contiguous with the major receptive field and are innervated by fine anterior and posterior axons, but there is no overlap between major and minor receptive fields. 2. At low frequencies of stimulation of the minor receptive fields, conduction block takes place in the mP cell at the central branch point within the leech ganglion. 3. The mP cell synapses directly with many other cells in the leech ganglion, including the anterior pagoda (AP) cell, longitudinal (L) motoneurone and the annulus erector (AE) motoneurone, which were studied as a group of postsynaptic neurones. Conduction block in the mP cell affects its synaptic transmission to all three postsynaptic neurones, but the effect can be different in different postsynaptic neurones. Block at the central branch point for an impulse travelling along the anterior axon reduces transmission to the AE cell much more than to the AP or L cells, while block at the central branch for an impulse travelling along the posterior axon has the reverse effect. 4. The distribution of functional connections of the branches of the mP cell with each postsynaptic cell was studied. For this analysis, branches of the mP cell were selectively silenced either during conduction block or by laser microsurgery. Generally, nearly all of the functional connections with the L and AP cell are made by anterior branches of the mP cell while the connection with the AE cell was primarily made by posterior branches of the mP cell. 5. The possible sites of contact between the mP cell and postsynaptic cells were determined by injecting separate markers into the mP cell and a postsynaptic cell. In confirmation of physiology, the mP cell's posterior branches had few, if any

  8. Dynamical Mapping of Anopheles darlingi Densities in a Residual Malaria Transmission Area of French Guiana by Using Remote Sensing and Meteorological Data

    PubMed Central

    Adde, Antoine; Roux, Emmanuel; Mangeas, Morgan; Dessay, Nadine; Nacher, Mathieu; Dusfour, Isabelle; Girod, Romain; Briolant, Sébastien

    2016-01-01

    Local variation in the density of Anopheles mosquitoes and the risk of exposure to bites are essential to explain the spatial and temporal heterogeneities in the transmission of malaria. Vector distribution is driven by environmental factors. Based on variables derived from satellite imagery and meteorological observations, this study aimed to dynamically model and map the densities of Anopheles darlingi in the municipality of Saint-Georges de l’Oyapock (French Guiana). Longitudinal sampling sessions of An. darlingi densities were conducted between September 2012 and October 2014. Landscape and meteorological data were collected and processed to extract a panel of variables that were potentially related to An. darlingi ecology. Based on these data, a robust methodology was formed to estimate a statistical predictive model of the spatial-temporal variations in the densities of An. darlingi in Saint-Georges de l’Oyapock. The final cross-validated model integrated two landscape variables—dense forest surface and built surface—together with four meteorological variables related to rainfall, evapotranspiration, and the minimal and maximal temperatures. Extrapolation of the model allowed the generation of predictive weekly maps of An. darlingi densities at a resolution of 10-m. Our results supported the use of satellite imagery and meteorological data to predict malaria vector densities. Such fine-scale modeling approach might be a useful tool for health authorities to plan control strategies and social communication in a cost-effective, targeted, and timely manner. PMID:27749938

  9. Properties of Transmission and Leaky Modes in a Plasmonic Waveguide Constructed by Periodic Subwavelength Metallic Hollow Blocks

    NASA Astrophysics Data System (ADS)

    Jei Wu, Jin; Jang Wu, Chien; Qi Shen, Jian; Hou, Da Jun; Chen Lo, Wen

    2015-09-01

    Based on the concept of low-frequency spoof surface plasmon polaritons (spoof SPPs), a kind of leaky mode is proposed in a waveguide made of a subwavelength metal-block array with open slots. Numerical results reveal that a new transmission mode is found in the periodic subwavelength metal open blocks. This modal field is located inside the interior of a hollow block compared with that in a solid metal block array. The dispersion curve shows that such a new SPPs mode has a negative slope, crossing the light line, and then going into a zone of leaky mode at higher frequencies. The leaky mode has a wider frequency bandwidth, and this can lead to a radiation scanning angle of 53° together with high radiation efficiency. Based on the individual characteristics exhibited by a frequency-dependent radiation pattern for the present leaky mode, the waveguide structure can have potential applications such as frequency dividers and demultiplexers. Experimental verification of such a leaky mode at microwave has been performed, and the experimental results are found to be consistent with the theoretical analysis.

  10. Properties of Transmission and Leaky Modes in a Plasmonic Waveguide Constructed by Periodic Subwavelength Metallic Hollow Blocks

    PubMed Central

    Jei Wu, Jin; Jang Wu, Chien; Qi Shen, Jian; Hou, Da Jun; Chen Lo, Wen

    2015-01-01

    Based on the concept of low-frequency spoof surface plasmon polaritons (spoof SPPs), a kind of leaky mode is proposed in a waveguide made of a subwavelength metal-block array with open slots. Numerical results reveal that a new transmission mode is found in the periodic subwavelength metal open blocks. This modal field is located inside the interior of a hollow block compared with that in a solid metal block array. The dispersion curve shows that such a new SPPs mode has a negative slope, crossing the light line, and then going into a zone of leaky mode at higher frequencies. The leaky mode has a wider frequency bandwidth, and this can lead to a radiation scanning angle of 53° together with high radiation efficiency. Based on the individual characteristics exhibited by a frequency-dependent radiation pattern for the present leaky mode, the waveguide structure can have potential applications such as frequency dividers and demultiplexers. Experimental verification of such a leaky mode at microwave has been performed, and the experimental results are found to be consistent with the theoretical analysis. PMID:26403387

  11. [Malaria in the Rostov Region: retrospective analysis of the malaria situation in 1952-2007].

    PubMed

    Kormilenko, I V; Aĭdinov, G T; Shvager, M M

    2009-01-01

    In the Rostov Region, no cases of local malaria transmission have been notified since 1958, but cases of import malaria are recorded every year. The region is one of malaria-susceptible areas in the Russian Federation, which is characterized by intensive migration, the malariogenic potential sufficient for local transmission (malariogenic index 1.2), and the optimum conditions for resurgence of malaria when it is imported. The prevention of undesirable consequences of malaria importation requires the strict monitoring of feverish patients, cohorts of high-risk patients who go for trips to malaria-endemic countries.

  12. Vaccine approaches to malaria control and elimination: Insights from mathematical models.

    PubMed

    White, Michael T; Verity, Robert; Churcher, Thomas S; Ghani, Azra C

    2015-12-22

    A licensed malaria vaccine would provide a valuable new tool for malaria control and elimination efforts. Several candidate vaccines targeting different stages of the malaria parasite's lifecycle are currently under development, with one candidate, RTS,S/AS01 for the prevention of Plasmodium falciparum infection, having recently completed Phase III trials. Predicting the public health impact of a candidate malaria vaccine requires using clinical trial data to estimate the vaccine's efficacy profile--the initial efficacy following vaccination and the pattern of waning of efficacy over time. With an estimated vaccine efficacy profile, the effects of vaccination on malaria transmission can be simulated with the aid of mathematical models. Here, we provide an overview of methods for estimating the vaccine efficacy profiles of pre-erythrocytic vaccines and transmission-blocking vaccines from clinical trial data. In the case of RTS,S/AS01, model estimates from Phase II clinical trial data indicate a bi-phasic exponential profile of efficacy against infection, with efficacy waning rapidly in the first 6 months after vaccination followed by a slower rate of waning over the next 4 years. Transmission-blocking vaccines have yet to be tested in large-scale Phase II or Phase III clinical trials so we review ongoing work investigating how a clinical trial might be designed to ensure that vaccine efficacy can be estimated with sufficient statistical power. Finally, we demonstrate how parameters estimated from clinical trials can be used to predict the impact of vaccination campaigns on malaria using a mathematical model of malaria transmission.

  13. The transmission potential of malaria-infected mosquitoes (An.gambiae-Keele, An.arabiensis-Ifakara) is altered by the vertebrate blood type they consume during parasite development.

    PubMed

    Emami, S Noushin; Ranford-Cartwright, Lisa C; Ferguson, Heather M

    2017-01-17

    The efficiency of malaria parasite development within mosquito vectors (sporogony) is a critical determinant of transmission. Sporogony is thought to be controlled by environmental conditions and mosquito/parasite genetic factors, with minimal contribution from mosquito behaviour during the period of parasite development. We tested this assumption by investigating whether successful sporogony of Plasmodium falciparum parasites through to human-infectious transmission stages is influenced by the host species upon which infected mosquitoes feed. Studies were conducted on two major African vector species that generally are found to differ in their innate host preferences: Anopheles arabiensis and An. gambiae sensu stricto. We show that the proportion of vectors developing transmissible infections (sporozoites) was influenced by the source of host blood consumed during sporogony. The direction of this effect was associated with the innate host preference of vectors: higher sporozoite prevalences were generated in the usually human-specialist An. gambiae s.s. feeding on human compared to cow blood, whereas the more zoophilic An. arabiensis had significantly higher prevalences after feeding on cow blood. The potential epidemiological implications of these results are discussed.

  14. The transmission potential of malaria-infected mosquitoes (An.gambiae-Keele, An.arabiensis-Ifakara) is altered by the vertebrate blood type they consume during parasite development

    PubMed Central

    Emami, S. Noushin; Ranford-Cartwright, Lisa C.; Ferguson, Heather M.

    2017-01-01

    The efficiency of malaria parasite development within mosquito vectors (sporogony) is a critical determinant of transmission. Sporogony is thought to be controlled by environmental conditions and mosquito/parasite genetic factors, with minimal contribution from mosquito behaviour during the period of parasite development. We tested this assumption by investigating whether successful sporogony of Plasmodium falciparum parasites through to human-infectious transmission stages is influenced by the host species upon which infected mosquitoes feed. Studies were conducted on two major African vector species that generally are found to differ in their innate host preferences: Anopheles arabiensis and An. gambiae sensu stricto. We show that the proportion of vectors developing transmissible infections (sporozoites) was influenced by the source of host blood consumed during sporogony. The direction of this effect was associated with the innate host preference of vectors: higher sporozoite prevalences were generated in the usually human-specialist An. gambiae s.s. feeding on human compared to cow blood, whereas the more zoophilic An. arabiensis had significantly higher prevalences after feeding on cow blood. The potential epidemiological implications of these results are discussed. PMID:28094293

  15. Mathematical evaluation of community level impact of combining bed nets and indoor residual spraying upon malaria transmission in areas where the main vectors are Anopheles arabiensis mosquitoes

    PubMed Central

    2013-01-01

    Background Indoor residual insecticide spraying (IRS) and long-lasting insecticide treated nets (LLINs) are commonly used together even though evidence that such combinations confer greater protection against malaria than either method alone is inconsistent. Methods A deterministic model of mosquito life cycle processes was adapted to allow parameterization with results from experimental hut trials of various combinations of untreated nets or LLINs (Olyset®, PermaNet 2.0®, Icon Life® nets) with IRS (pirimiphos methyl, lambda cyhalothrin, DDT), in a setting where vector populations are dominated by Anopheles arabiensis, so that community level impact upon malaria transmission at high coverage could be predicted. Results Intact untreated nets alone provide equivalent personal protection to all three LLINs. Relative to IRS plus untreated nets, community level protection is slightly higher when Olyset® or PermaNet 2.0® nets are added onto IRS with pirimiphos methyl or lambda cyhalothrin but not DDT, and when Icon Life® nets supplement any of the IRS insecticides. Adding IRS onto any net modestly enhances communal protection when pirimiphos methyl is sprayed, while spraying lambda cyhalothrin enhances protection for untreated nets but not LLINs. Addition of DDT reduces communal protection when added to LLINs. Conclusions Where transmission is mediated primarily by An. arabiensis, adding IRS to high LLIN coverage provides only modest incremental benefit (e.g. when an organophosphate like pirimiphos methyl is used), but can be redundant (e.g. when a pyrethroid like lambda cyhalothin is used) or even regressive (e.g. when DDT is used for the IRS). Relative to IRS plus untreated nets, supplementing IRS with LLINs will only modestly improve community protection. Beyond the physical protection that intact nets provide, additional protection against transmission by An. arabiensis conferred by insecticides will be remarkably small, regardless of whether they are delivered

  16. Blocking and transmission of traveling flow-distributed-oscillation waves in an absolutely unstable flowing medium.

    PubMed

    McGraw, Patrick N; Menzinger, Michael

    2012-08-01

    For a flowing, self-oscillating medium, we study the competition between traveling flow-distributed-oscillation waves excited by periodic driving at the upstream boundary and bulk oscillations originating downstream from the boundary. As previously observed in the case of stationary driving, we find that there is a region in parameter space where boundary-driven traveling waves of sufficiently high amplitude can impose themselves on the entire medium despite the presence of an absolute instability, which otherwise tends to block information from upstream. For sufficiently low flow rates, however, the imposed waves are arrested at a nonlinear blocking transition. Unlike the stationary case, we find that the region of imposed waves extends well into regions where, according to the linear approximation, there should be no traveling waves at all. This suggests that the extinction of the traveling waves is analogous to a subcritical Hopf bifurcation.

  17. Is there an efficient trap or collection method for sampling Anopheles darlingi and other malaria vectors that can describe the essential parameters affecting transmission dynamics as effectively as human landing catches? - A Review

    PubMed Central

    Lima, José Bento Pereira; Rosa-Freitas, Maria Goreti; Rodovalho, Cynara Melo; Santos, Fátima; Lourenço-de-Oliveira, Ricardo

    2014-01-01

    Distribution, abundance, feeding behaviour, host preference, parity status and human-biting and infection rates are among the medical entomological parameters evaluated when determining the vector capacity of mosquito species. To evaluate these parameters, mosquitoes must be collected using an appropriate method. Malaria is primarily transmitted by anthropophilic and synanthropic anophelines. Thus, collection methods must result in the identification of the anthropophilic species and efficiently evaluate the parameters involved in malaria transmission dynamics. Consequently, human landing catches would be the most appropriate method if not for their inherent risk. The choice of alternative anopheline collection methods, such as traps, must consider their effectiveness in reproducing the efficiency of human attraction. Collection methods lure mosquitoes by using a mixture of olfactory, visual and thermal cues. Here, we reviewed, classified and compared the efficiency of anopheline collection methods, with an emphasis on Neotropical anthropophilic species, especially Anopheles darlingi, in distinct malaria epidemiological conditions in Brazil. PMID:25185008

  18. Blocking of Plasmodium transmission by cooperative action of Cecropin A and Defensin A in transgenic Aedes aegypti mosquitoes.

    PubMed

    Kokoza, Vladimir; Ahmed, Abdouelaziz; Woon Shin, Sang; Okafor, Nwando; Zou, Zhen; Raikhel, Alexander S

    2010-05-04

    To overcome burden of mosquito-borne diseases, multiple control strategies are needed. Population replacement with genetically modified mosquitoes carrying antipathogen effector genes is one of the possible approaches for controlling disease transmission. However, transgenic mosquitoes with antipathogen phenotypes based on overexpression of a single type effector molecule are not efficient in interrupting pathogen transmission. Here, we show that co-overexpression of two antimicrobial peptides (AMP), Cecropin A, and Defensin A, in transgenic Aedes aegypti mosquitoes results in the cooperative antibacterial and antiPlasmodium action of these AMPs. The transgenic hybrid mosquitoes that overexpressed both Cecropin A and Defensin A under the control of the vitellogenin promoter exhibited an elevated resistance to Pseudomonas aeruginosa infection, indicating that these AMPs acted cooperatively against this pathogenic bacterium. In these mosquitoes infected with P. gallinaceum, the number of oocysts was dramatically reduced in midguts, and no sporozoites were found in their salivary glands when the mosquitoes were fed twice to reactivate transgenic AMP production. Infection experiments using the transgenic hybrid mosquitoes, followed by sequential feeding on naive chicken, and then naive wild-type mosquitoes showed that the Plasmodium transmission was completely blocked. This study suggests an approach in generating transgenic mosquitoes with antiPlasmodium refractory phenotype, which is coexpression of two or more effector molecules with cooperative action on the parasite.

  19. Seasonal population changes and malaria transmission potential of Anopheles pharoensis and the minor anophelines in Mwea Irrigation Scheme, Kenya.

    PubMed

    Mukiama, T K; Mwangi, R W

    1989-05-01

    A study in 1984 and 1985 showed that Anopheles gambiae s.l. and An. pharoensis were the major anophelines in Mwea Irrigation Scheme, Kenya, constituting 83.86% and 15.69% of the catch respectively. Four minor species made up the remaining 0.45%. The irrigation phase of the rice cultivation cycle in August, which linked the flooding effects of the two rainy seasons, resulted in major population increases of An. pharoensis and enabled continuous breeding for up to 9 months per year. The average of mean monthly proportions of unfed, bloodfed, and gravid females was 26.6, 58.8, and 14.6% respectively. The Plasmodium falciparum sporozoite rates for An. pharoensis were 1.3% by ELISA and 0.68% by dissection, while those for An. funestus were 1.7% by ELISA and 1.25% by dissection. An. pharoensis can contribute to the epidemiology of Malaria in the Mwea area.

  20. Malaria transmission and insecticide resistance of Anopheles gambiae (Diptera: Culicidae) in the French military camp of Port-Bouët, Abidjan (Côte d'Ivoire): implications for vector control.

    PubMed

    Girod, Romain; Orlandi-Pradines, Eve; Rogier, Christophe; Pages, Frederic

    2006-09-01

    An important vector control program is ongoing to lower the risk of malaria transmission in the French military camp of Port-Bouët, Abidjan (Côte d'Ivoire). However, some autochthonous malaria cases are regularly suspected. An entomological survey was conducted in June 2004 in the camp to assess malaria transmission and evaluate the pyrethroid and organophosphate resistance of the malaria vectors. The average mosquito biting rate was 178.0 bites per person per night. Mosquitoes belonging to the Anopheles gambiae (Diptera: Culicidae) complex and the Anopheles funestus group were collected. An. gambiae s.s. molecular form M was the only species of the An. gambiae complex present. The average number of An. gambiae bites was approximately 44.3 per person per night. The circumsporozoite index was 0.38% and the entomological inoculation rate estimated to be 1.2 infective bites per week for the study period. The kdr and ace1 gene frequencies in the An. gambiae population were 0.70 and 0.15, respectively. Personnel living in the French barracks of Port-Bouët are thus at high risk of being bitten by parasite-infected mosquitoes. Such an entomological inoculation rate, usually found in African peri-urban environments, was unexpected considering the extensive effort deployed to control mosquitoes in the camp. Insecticide resistance could explain the inefficacy of the vector control program but the spraying strategy is also questionable.

  1. Anopheles (Kerteszia) cruzii (DIPTERA: CULICIDAE) IN PERIDOMICILIARY AREA DURING ASYMPTOMATIC MALARIA TRANSMISSION IN THE ATLANTIC FOREST: MOLECULAR IDENTIFICATION OF BLOOD-MEAL SOURCES INDICATES HUMANS AS PRIMARY INTERMEDIATE HOSTS

    PubMed Central

    Kirchgatter, Karin; Tubaki, Rosa Maria; Malafronte, Rosely dos Santos; Alves, Isabel Cristina; Lima, Giselle Fernandes Maciel de Castro; Guimarães, Lilian de Oliveira; Zampaulo, Robson de Almeida; Wunderlich, Gerhard

    2014-01-01

    Anopheles (Kerteszia) cruzii has been implicated as the primary vector of human and simian malarias out of the Brazilian Amazon and specifically in the Atlantic Forest regions. The presence of asymptomatic human cases, parasite-positive wild monkeys and the similarity between the parasites infecting them support the discussion whether these infections can be considered as a zoonosis. Although many aspects of the biology of An. cruzii have already been addressed, studies conducted during outbreaks of malaria transmission, aiming at the analysis of blood feeding and infectivity, are missing in the Atlantic Forest. This study was conducted in the location of Palestina, Juquitiba, where annually the majority of autochthonous human cases are notified in the Atlantic Forest of the state of São Paulo. Peridomiciliary sites were selected for collection of mosquitoes in a perimeter of up to 100 m around the residences of human malaria cases. The mosquitoes were analyzed with the purpose of molecular identification of blood-meal sources and to examine the prevalence of Plasmodium. A total of 13,441 females of An. (Ker.) cruzii were collected. The minimum infection rate was calculated at 0.03% and 0.01%, respectively, for P. vivax and P. malariae and only human blood was detected in the blood-fed mosquitoes analyzed. This data reinforce the hypothesis that asymptomatic human carriers are the main source of anopheline infection in the peridomiciliary area, making the probability of zoonotic transmission less likely to happen. PMID:25229220

  2. Temperature alters Plasmodium blocking by Wolbachia

    NASA Astrophysics Data System (ADS)

    Murdock, Courtney C.; Blanford, Simon; Hughes, Grant L.; Rasgon, Jason L.; Thomas, Matthew B.

    2014-02-01

    Very recently, the Asian malaria vector (Anopheles stephensi) was stably transinfected with the wAlbB strain of Wolbachia, inducing refractoriness to the human malaria parasite Plasmodium falciparum. However, conditions in the field can differ substantially from those in the laboratory. We use the rodent malaria P. yoelii, and somatically transinfected An. stephensi as a model system to investigate whether the transmission blocking potential of wAlbB is likely to be robust across different thermal environments. wAlbB reduced malaria parasite prevalence and oocyst intensity at 28°C. At 24°C there was no effect on prevalence but a marked increase in oocyst intensity. At 20°C, wAlbB had no effect on prevalence or intensity. Additionally, we identified a novel effect of wAlbB that resulted in reduced sporozoite development across temperatures, counterbalancing the oocyst enhancement at 24°C. Our results demonstrate complex effects of temperature on the Wolbachia-malaria interaction, and suggest the impacts of transinfection might vary across diverse environments.

  3. Synergistic and antagonistic interactions between bednets and vaccines in the control of malaria

    PubMed Central

    Artzy-Randrup, Yael; Dobson, Andrew P.; Pascual, Mercedes

    2015-01-01

    It is extremely likely that the malaria vaccines currently in development will be used in conjunction with treated bednets and other forms of malaria control. The interaction of different intervention methods is at present poorly understood in a disease such as malaria where immunity is more complex than for other pathogens that have been successfully controlled by vaccination. Here we develop a general mathematical model of malaria transmission to examine the interaction between vaccination and bednets. Counterintuitively, we find that the frailty of malaria immunity will potentially cause both synergistic and antagonistic interactions between vaccination and the use of bednets. We explore the conditions that create these tensions, and outline strategies that minimize their detrimental impact. Our analysis specifically considers the three leading vaccine classes currently in development: preerythrocytic (PEV), blood stage (BSV), and transmission blocking (TBV). We find that the combination of BSV with treated bednets can lead to increased morbidity with no added value in terms of elimination; the interaction is clearly antagonistic. In contrast, there is strong synergy between PEV and treated bednets that may facilitate elimination, although transient stages are likely to increase morbidity. The combination of TBV with treated bednets is synergistic, lowering both morbidity and elimination thresholds. Our results suggest that vaccines will not provide a straightforward solution to malaria control, and that future programs need to consider the synergistic and antagonistic interactions between vaccines and treated bednets. PMID:25605894

  4. Lethal and Pre-Lethal Effects of a Fungal Biopesticide Contribute to Substantial and Rapid Control of Malaria Vectors

    PubMed Central

    Blanford, Simon; Shi, Wangpeng; Christian, Riann; Marden, James H.; Koekemoer, Lizette L.; Brooke, Basil D.; Coetzee, Maureen; Read, Andrew F.; Thomas, Matthew B.

    2011-01-01

    Rapidly emerging insecticide resistance is creating an urgent need for new active ingredients to control the adult mosquitoes that vector malaria. Biopesticides based on the spores of entomopathogenic fungi have shown considerable promise by causing very substantial mortality within 7–14 days of exposure. This mortality will generate excellent malaria control if there is a high likelihood that mosquitoes contact fungi early in their adult lives. However, where contact rates are lower, as might result from poor pesticide coverage, some mosquitoes will contact fungi one or more feeding cycles after they acquire malaria, and so risk transmitting malaria before the fungus kills them. Critics have argued that ‘slow acting’ fungal biopesticides are, therefore, incapable of delivering malaria control in real-world contexts. Here, utilizing standard WHO laboratory protocols, we demonstrate effective action of a biopesticide much faster than previously reported. Specifically, we show that transient exposure to clay tiles sprayed with a candidate biopesticide comprising spores of a natural isolate of Beauveria bassiana, could reduce malaria transmission potential to zero within a feeding cycle. The effect resulted from a combination of high mortality and rapid fungal-induced reduction in feeding and flight capacity. Additionally, multiple insecticide-resistant lines from three key African malaria vector species were completely susceptible to fungus. Thus, fungal biopesticides can block transmission on a par with chemical insecticides, and can achieve this where chemical insecticides have little impact. These results support broadening the current vector control paradigm beyond fast-acting chemical toxins. PMID:21897846

  5. Characterizing the Three-Dimensional Structure of Block Copolymers via Sequential Infiltration Synthesis and Scanning Transmission Electron Tomography.

    PubMed

    Segal-Peretz, Tamar; Winterstein, Jonathan; Doxastakis, Manolis; Ramírez-Hernández, Abelardo; Biswas, Mahua; Ren, Jiaxing; Suh, Hyo Seon; Darling, Seth B; Liddle, J Alexander; Elam, Jeffrey W; de Pablo, Juan J; Zaluzec, Nestor J; Nealey, Paul F

    2015-05-26

    Understanding and controlling the three-dimensional structure of block copolymer (BCP) thin films is critical for utilizing these materials for sub-20 nm nanopatterning in semiconductor devices, as well as in membranes and solar cell applications. Combining an atomic layer deposition (ALD)-based technique for enhancing the contrast of BCPs in transmission electron microscopy (TEM) together with scanning TEM (STEM) tomography reveals and characterizes the three-dimensional structures of poly(styrene-block-methyl methacrylate) (PS-b-PMMA) thin films with great clarity. Sequential infiltration synthesis (SIS), a block-selective technique for growing inorganic materials in BCPs films in an ALD tool and an emerging technique for enhancing the etch contrast of BCPs, was harnessed to significantly enhance the high-angle scattering from the polar domains of BCP films in the TEM. The power of combining SIS and STEM tomography for three-dimensional (3D) characterization of BCP films was demonstrated with the following cases: self-assembled cylindrical, lamellar, and spherical PS-b-PMMA thin films. In all cases, STEM tomography has revealed 3D structures that were hidden underneath the surface, including (1) the 3D structure of defects in cylindrical and lamellar phases, (2) the nonperpendicular 3D surface of grain boundaries in the cylindrical phase, and (3) the 3D arrangement of spheres in body-centered-cubic (BCC) and hexagonal-closed-pack (HCP) morphologies in the spherical phase. The 3D data of the spherical morphologies was compared to coarse-grained simulations and assisted in validating the simulations' parameters. STEM tomography of SIS-treated BCP films enables the characterization of the exact structure used for pattern transfer and can lead to a better understating of the physics that is utilized in BCP lithography.

  6. Hemolytic C-type lectin CEL-III from sea cucumber expressed in transgenic mosquitoes impairs malaria parasite development.

    PubMed

    Yoshida, Shigeto; Shimada, Yohei; Kondoh, Daisuke; Kouzuma, Yoshiaki; Ghosh, Anil K; Jacobs-Lorena, Marcelo; Sinden, Robert E

    2007-12-01

    The midgut environment of anopheline mosquitoes plays an important role in the development of the malaria parasite. Using genetic manipulation of anopheline mosquitoes to change the environment in the mosquito midgut may inhibit development of the malaria parasite, thus blocking malaria transmission. Here we generate transgenic Anopheles stephensi mosquitoes that express the C-type lectin CEL-III from the sea cucumber, Cucumaria echinata, in a midgut-specific manner. CEL-III has strong and rapid hemolytic activity toward human and rat erythrocytes in the presence of serum. Importantly, CEL-III binds to ookinetes, leading to strong inhibition of ookinete formation in vitro with an IC(50) of 15 nM. Thus, CEL-III exhibits not only hemolytic activity but also cytotoxicity toward ookinetes. In these transgenic mosquitoes, sporogonic development of Plasmodium berghei is severely impaired. Moderate, but significant inhibition was found against Plasmodium falciparum. To our knowledge, this is the first demonstration of stably engineered anophelines that affect the Plasmodium transmission dynamics of human malaria. Although our laboratory-based research does not have immediate applications to block natural malaria transmission, these findings have significant implications for the generation of refractory mosquitoes to all species of human Plasmodium and elucidation of mosquito-parasite interactions.

  7. FOSL1 Inhibits Type I Interferon Responses to Malaria and Viral Infections by Blocking TBK1 and TRAF3/TRIF Interactions

    PubMed Central

    Cai, Baowei; Wu, Jian; Yu, Xiao

    2017-01-01

    ABSTRACT Innate immune response plays a critical role in controlling invading pathogens, but such an immune response must be tightly regulated. Insufficient or overactivated immune responses may lead to harmful or even fatal consequences. To dissect the complex host-parasite interactions and the molecular mechanisms underlying innate immune responses to infections, here we investigate the role of FOS-like antigen 1 (FOSL1) in regulating the host type I interferon (IFN-I) response to malaria parasite and viral infections. FOSL1 is known as a component of a transcription factor but was recently implicated in regulating the IFN-I response to malaria parasite infection. Here we show that FOSL1 can act as a negative regulator of IFN-I signaling. Upon stimulation with poly(I:C), malaria parasite-infected red blood cells (iRBCs), or vesicular stomatitis virus (VSV), FOSL1 “translocated” from the nucleus to the cytoplasm, where it inhibited the interactions between TNF receptor-associated factor 3 (TRAF3), TIR domain-containing adapter inducing IFN-β (TRIF), and Tank-binding kinase 1 (TBK1) via impairing K63-linked polyubiquitination of TRAF3 and TRIF. Importantly, FOSL1 knockout chimeric mice had lower levels of malaria parasitemia or VSV titers in peripheral blood and decreased mortality compared with wild-type (WT) mice. Thus, our findings have identified a new role for FOSL1 in negatively regulating the host IFN-I response to malaria and viral infections and have identified a potential drug target for controlling malaria and other diseases. PMID:28049150

  8. Naturally Acquired Antibody Responses to Plasmodium vivax and Plasmodium falciparum Merozoite Surface Protein 1 (MSP1) C-Terminal 19 kDa Domains in an Area of Unstable Malaria Transmission in Southeast Asia.

    PubMed

    Wang, Qinghui; Zhao, Zhenjun; Zhang, Xuexing; Li, Xuelian; Zhu, Min; Li, Peipei; Yang, Zhaoqing; Wang, Ying; Yan, Guiyun; Shang, Hong; Cao, Yaming; Fan, Qi; Cui, Liwang

    2016-01-01

    Understanding naturally acquired immunity to infections caused by Plasmodia in different malaria endemicity settings is needed for better vaccine designs and for exploring antibody responses as a proxy marker of malaria transmission intensity. This study investigated the sero-epidemiology of malaria along the international border between China and Myanmar, where malaria elimination action plans are in place. This study recruited 233 P. vivax and 156 P. falciparum infected subjects with acute malaria at the malaria clinics and hospitals. In addition, 93 and 67 healthy individuals from the same endemic region or from non-endemic region, respectively, were used as controls. Acute malaria infections were identified by microscopy. Anti-recombinant PfMSP119 and PvMSP119 antibody levels were measured by ELISA. Antibody responses to respective MSP119 were detected in 50.9% and 78.2% patients with acute P. vivax and P. falciparum infections, respectively. There were cross-reacting antibodies in Plasmodium patients against these two recombinant proteins, though we could not exclude the possibility of submicroscopic mixed-species infections. IgG1, IgG3 and IgG4 were the major subclasses. Interestingly, 43.2% of the healthy endemic population also had antibodies against PfMSP119, whereas only 3.9% of this population had antibodies against PvMSP119. Higher antibody levels were correlated with age and parasite density, but not with season, gender or malaria history. Both total IgG and individual IgG subclasses underwent substantial declines during the convalescent period in three months. This study demonstrated that individuals in a hypoendemic area with coexistence of P. vivax and P. falciparum can mount rapid antibody responses against both PfMSP119 and PvMSP119. The significantly higher proportion of responders to PfMSP119 in the healthy endemic population indicates higher prevalence of P. falciparum in the recent past. Specific antibodies against PvMSP119 could serve as a

  9. Naturally Acquired Antibody Responses to Plasmodium vivax and Plasmodium falciparum Merozoite Surface Protein 1 (MSP1) C-Terminal 19 kDa Domains in an Area of Unstable Malaria Transmission in Southeast Asia

    PubMed Central

    Wang, Qinghui; Zhao, Zhenjun; Zhang, Xuexing; Li, Xuelian; Zhu, Min; Li, Peipei; Yang, Zhaoqing; Wang, Ying; Yan, Guiyun; Shang, Hong; Cao, Yaming; Fan, Qi; Cui, Liwang

    2016-01-01

    Understanding naturally acquired immunity to infections caused by Plasmodia in different malaria endemicity settings is needed for better vaccine designs and for exploring antibody responses as a proxy marker of malaria transmission intensity. This study investigated the sero-epidemiology of malaria along the international border between China and Myanmar, where malaria elimination action plans are in place. This study recruited 233 P. vivax and 156 P. falciparum infected subjects with acute malaria at the malaria clinics and hospitals. In addition, 93 and 67 healthy individuals from the same endemic region or from non-endemic region, respectively, were used as controls. Acute malaria infections were identified by microscopy. Anti-recombinant PfMSP119 and PvMSP119 antibody levels were measured by ELISA. Antibody responses to respective MSP119 were detected in 50.9% and 78.2% patients with acute P. vivax and P. falciparum infections, respectively. There were cross-reacting antibodies in Plasmodium patients against these two recombinant proteins, though we could not exclude the possibility of submicroscopic mixed-species infections. IgG1, IgG3 and IgG4 were the major subclasses. Interestingly, 43.2% of the healthy endemic population also had antibodies against PfMSP119, whereas only 3.9% of this population had antibodies against PvMSP119. Higher antibody levels were correlated with age and parasite density, but not with season, gender or malaria history. Both total IgG and individual IgG subclasses underwent substantial declines during the convalescent period in three months. This study demonstrated that individuals in a hypoendemic area with coexistence of P. vivax and P. falciparum can mount rapid antibody responses against both PfMSP119 and PvMSP119. The significantly higher proportion of responders to PfMSP119 in the healthy endemic population indicates higher prevalence of P. falciparum in the recent past. Specific antibodies against PvMSP119 could serve as a

  10. A spatial individual-based model predicting a great impact of copious sugar sources and resting sites on survival of Anopheles gambiae and malaria parasite transmission

    USGS Publications Warehouse

    Zhu, Lin; Qualls, Whitney A.; Marshall, John M; Arheart, Kris L.; DeAngelis, Don; McManus, John W.; Traore, Sekou F.; Doumbia, Seydou; Schlein, Yosef; Muller, Gunter C.; Beier, John C.

    2015-01-01

    distributed in the whole village compared to clustering around outdoor resting sites or houses.ConclusionsIncreases in densities of sugar sources or outdoor resting sites significantly increase the survival and human biting rates of An. gambiae mosquitoes. Survival of An. gambiae is more supported by random distribution of sugar sources than clustering of sugar sources around resting sites or houses. Density and spatial distribution of natural sugar sources and outdoor resting sites modulate vector populations and human biting rates, and thus malaria parasite transmission.

  11. Imported malaria.

    PubMed

    Schultz, M G

    1974-01-01

    There have been 4 waves of imported malaria in the USA. They occurred during the colonization of the country and during the Second World War, the UN Police Action in Korea, and the Viet-Nam conflict. The first 3 episodes are briefly described and the data on imported malaria from Viet-Nam are discussed in detail.Endemic malaria is resurgent in many tropical countries and international travel is also on the rise. This increases the likelihood of malaria being imported from an endemic area and introduced into a receptive area. The best defence for countries threatened by imported malaria is a vigorous surveillance programme. The principles of surveillance are discussed and an example of their application is provided by a description of the methods used to conduct surveillance of malaria in the USA.

  12. [Malaria in the Americas].

    PubMed

    Carme, B; Venturin, C

    1999-01-01

    In 1996, malaria involving Plasmodium vivax, Plasmodium falciparum, and, to a lesser extent, Plasmodium malariae was endemic in 21 countries in the Americas. The Amazon river basin and bordering areas including the Guyanas were the most affected zones. Until the mid 1970s, endemic malaria appeared to be under control. However in the ensuing 15 year period, the situation deteriorated drastically. Although trends varied depending on location, aggregate indexes indicated a twofold increase with recrudescence in previously settled areas and emergence in newly populated zones. Since 1990, the situation has worsened further in some areas where increased incidences have been associated with a high levels of drug-resistant Plasmodium falciparum. However this species remains in minority except in the Guyanas where the highest annual incidences (100 to 500 cases per 1000) and the most drug-resistant Plasmodium have been reported. The causes underlying this deterioration are numerous and complex. In regions naturally prone to transmission of the disease, outbreaks have been intensified by unrestrained settlement. The resulting deforestation has created new breeding areas for Anopheles darlingi, the main vector of malaria in the Americas. Migration of poor populations to newly opened farming and mining areas has created highly exposed areas for malaria infection. Implementation of adequate medical care and prevention measures has been hindered by a lack of money and sociopolitical unrest. Climatic phenomenon related the El Nino have also been favorable to the return of malaria to the region. Except with regard to financial resources and political unrest, the same risk factors for malaria are present in French Guiana.

  13. Malaria Research

    MedlinePlus

    ... critical role in development of those next-generation strategies. Read more about malaria prevention, treatment and control Global Cooperation Collaboration involving scientists from diverse disciplines is ...

  14. Exosomes in human semen restrict HIV-1 transmission by vaginal cells and block intravaginal replication of LP-BM5 murine AIDS virus complex

    PubMed Central

    Madison, Marisa N.; Jones, Philip H.; Okeoma, Chioma M.

    2015-01-01

    Exosomes are membranous extracellular nanovesicles secreted by diverse cell types. Exosomes from healthy human semen have been shown to inhibit HIV-1 replication and to impair progeny virus infectivity. In this study, we examined the ability of healthy human semen exosomes to restrict HIV-1 and LP-BM5 murine AIDS virus transmission in three different model systems. We show that vaginal cells internalize exosomes with concomitant transfer of functional mRNA. Semen exosomes blocked the spread of HIV-1 from vaginal epithelial cells to target cells in our cell-to-cell infection model and suppressed transmission of HIV-1 across the vaginal epithelial barrier in our trans-well model. Our in vivo model shows that human semen exosomes restrict intravaginal transmission and propagation of murine AIDS virus. Our study highlights an antiretroviral role for semen exosomes that may be harnessed for the development of novel therapeutic strategies to combat HIV-1 transmission. PMID:25880110

  15. Nanovaccines for malaria using Plasmodium falciparum antigen Pfs25 attached gold nanoparticles.

    PubMed

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

    2015-09-22

    Malaria transmission-blocking vaccines (TBV) targeting sexual stages of the parasite represent an ideal intervention to reduce the burden of the disease and eventual elimination at the population level in endemic regions. Immune responses against sexual stage antigens impair the development of parasite inside the mosquitoes. Target antigens identified in Plasmodium falciparum include surface proteins Pfs230 and Pfs48/45 in male and female gametocytes and Pfs25 expressed in zygotes and ookinetes. The latter has undergone extensive evaluation in pre-clinical and phase I clinical trials and remains one of the leading target antigens for the development of TBV. Pfs25 has a complex tertiary structure characterized by four EGF-like repeat motifs formed by 11 disulfide bonds, and it has been rather difficult to obtain Pfs25 as a homogenous product in native conformation in any heterologous expression system. Recently, we have reported expression of codon-harmonized recombinant Pfs25 in Escherichia coli (CHrPfs25) and which elicited highly potent malaria transmission-blocking antibodies in mice. In the current study, we investigated CHrPfs25 along with gold nanoparticles of different shapes, size and physicochemical properties as adjuvants for induction of transmission blocking immunity. The results revealed that CHrPfs25 delivered with various gold nanoparticles elicited strong transmission blocking antibodies and suggested that gold nanoparticles based formulations can be developed as nanovaccines to enhance the immunogenicity of vaccine antigens.

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

    PubMed Central

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

    2015-01-01

    Malaria transmission-blocking vaccines (TBV) targeting sexual stages of the parasite represent an ideal intervention to reduce the burden of the disease and eventual elimination at the population level in endemic regions. Immune responses against sexual stage antigens impair the development of parasite inside the mosquitoes. Target antigens identified in Plasmodium falciparum include surface proteins Pfs230 and Pfs48/45 in male and female gametocytes and Pfs25 expressed in zygotes and ookinetes. The latter has undergone extensive evaluation in pre-clinical and phase I clinical trials and remains one of the leading target antigens for the development of TBV. Pfs25 has a complex tertiary structure characterized by four EGF-like repeat motifs formed by 11 disulfide bonds, and it has been rather difficult to obtain Pfs25 as a homogenous product in native conformation in any heterologous expression system. Recently, we have reported expression of codon-harmonized recombinant Pfs25 in E. coli (CHrPfs25) and which elicited highly potent malaria transmission-blocking antibodies in mice. In the current study, we investigated CHrPfs25 along with gold nanoparticles of different shapes, size and physicochemical properties as adjuvants for induction of transmission blocking immunity. The results revealed that CHrPfs25 delivered with various gold nanoparticles elicited strong transmission blocking antibodies and suggested that gold nanoparticles based formulations can be developed as nanovaccines to enhance the immunogenicity of vaccine antigens. PMID:26299750

  17. Eradicating malaria.

    PubMed

    Breman, Joel G

    2009-01-01

    The renewed interest in malaria research and control is based on the intolerable toll this disease takes on young children and pregnant women in Africa and other vulnerable populations; 150 to 300 children die each hour from malaria amounting to 1 to 2 million deaths yearly. Malaria-induced neurologic impairment, anemia, hypoglycemia, and low birth weight imperil normal development and survival. Resistance of Plasmodium falciparum to drugs and Anopheles mosquitoes to insecticides has stimulated discovery and development of artemisinin-based combination treatments (ACTs) and other drugs, long-lasting insecticide-treated bednets (with synthetic pyrethroids) and a search for non-toxic, long-lasting, affordable insecticides for indoor residual spraying (IRS). Malaria vaccine development and testing are progressing rapidly and a recombinant protein (RTS,S/AS02A) directed against the circumsporozoite protein is soon to be in Phase 3 trials. Support for malaria control, research, and advocacy through the Global Fund for HIV/AIDS, Tuberculosis and Malaria, the U.S. President's Malaria Initiative, the Bill & Melinda Gates Foundation, WHO and other organizations is resulting in decreasing morbidity and mortality in many malarious countries. Sustainability of effective programs through training and institution strengthening will be the key to malaria elimination coupled with improved surveillance and targeted research.

  18. Monoclonal And Single Domain Antibodies Targeting β-Integrin Subunits Block Sexual Transmission of HIV-1 in in vitro and in vivo Model Systems

    PubMed Central

    Guedon, Janet Tai; Luo, Kun; Zhang, Hong; Markham, Richard B.

    2015-01-01

    Background Poor adherence to prevention regimens for gel-based anti-HIV-1 microbicides has been a major obstacle to more effective pre-exposure prophylaxis. Concern persists that the antiretroviral drug containing microbicides might promote development of antiretroviral resistance. Methods Using in vitro transwell systems and a humanized mouse model of HIV-1 sexual transmission, we examined, as candidate microbicides, antibodies targeting the heterodimeric leukocyte function associated antigen 1 (LFA-1), a non-virally encoded protein acquired by the virus that also plays a critical role cell movement across endothelial and epithelial barriers. LFA-1 specific single domain variable regions from alpaca heavy-chain only antibodies (VHH) were identified and evaluated for their ability to inhibit HIV-1 transmission in the in vitro transwell system. Results Monoclonal antibodies targeting the CD11a and CD18 components of LFA-1 significantly reduced cell-free and cell-associated HIV-1 transmission in the in vitro transwell culture system and prevented virus transmission in the humanized mouse model of vaginal transmission. The broadly neutralizing monoclonal antibody b12 was unable to block transmission of cell-free virus. CD11a-specific VHH were isolated and expressed and the purified variable region protein domains reduced in vitro transepithelial transmission with an efficacy comparable to that of the CD11a monoclonal antibody. Conclusions Targeting integrins acquired by HIV-1 during budding and which are critical to interactions between epithelial cells and lymphocytes can reduce viral movement across epithelial barriers and prevent transmission in a humanized mouse model of sexual transmission. VHH capable of being produced by transformed bacteria can significantly reduce transepithelial virus transmission in in vitro model systems. PMID:25828964

  19. The impact of an intervention to introduce malaria rapid diagnostic tests on fever case management in a high transmission setting in Uganda: A mixed-methods cluster-randomized trial (PRIME)

    PubMed Central

    Chandler, Clare I. R.; Webb, Emily L.; Maiteki-Sebuguzi, Catherine; Nayiga, Susan; Nabirye, Christine; DiLiberto, Deborah D.; Ssemmondo, Emmanuel; Dorsey, Grant; Kamya, Moses R.; Staedke, Sarah G.

    2017-01-01

    Background Rapid diagnostic tests for malaria (mRDTs) have been scaled-up widely across Africa. The PRIME study evaluated an intervention aiming to improve fever case management using mRDTs at public health centers in Uganda. Methods A cluster-randomized trial was conducted from 2010–13 in Tororo, a high malaria transmission setting. Twenty public health centers were randomized in a 1:1 ratio to intervention or control. The intervention included training in health center management, fever case management with mRDTs, and patient-centered services; plus provision of mRDTs and artemether-lumefantrine (AL) when stocks ran low. Three rounds of Interviews were conducted with caregivers of children under five years of age as they exited health centers (N = 1400); reference mRDTs were done in children with fever (N = 1336). Health worker perspectives on mRDTs were elicited through semi-structured questionnaires (N = 49) and in-depth interviews (N = 10). The primary outcome was inappropriate treatment of malaria, defined as the proportion of febrile children who were not treated according to guidelines based on the reference mRDT. Findings There was no difference in inappropriate treatment of malaria between the intervention and control arms (24.0% versus 29.7%, adjusted risk ratio 0.81 [95% CI: 0.56, 1.17] p = 0.24). Most children (76.0%) tested positive by reference mRDT, but many were not prescribed AL (22.5% intervention versus 25.9% control, p = 0.53). Inappropriate treatment of children testing negative by reference mRDT with AL was also common (31.3% invention vs 42.4% control, p = 0.29). Health workers appreciated mRDTs but felt that integrating testing into practice was challenging given constraints on time and infrastructure. Conclusions The PRIME intervention did not have the desired impact on inappropriate treatment of malaria for children under five. In this high transmission setting, use of mRDTs did not lead to the reductions in antimalarial prescribing

  20. Imported malaria in Kuwait.

    PubMed

    Hira, P R; Behbehani, K; Al-Kandari, S

    1985-01-01

    The number of imported malaria cases in Kuwait rose from 87 in 1980 to 504 in 1983, an increase of 579%. The continued resurgence of malaria in endemic zones, improved diagnostic techniques and a heightened awareness of imported malaria have contributed to the increase in the number of microscopically proved cases. Thick blood films fixed in acetone and stained in Giemsa proved a rapid method of diagnosis; species identification on the basis of a thin film on the same slide was performed with ease. Malaria was acquired in 38 countries. Most patients were young male adults. Most of the cases were due to Plasmodium vivax originating from India, although an increasing number of P. falciparum cases are also now being diagnosed from there. P. falciparum infections were evenly distributed throughout the year and most cases presented within 14 days of their arrival in the country. The highest number of P. vivax cases were diagnosed between May and October, when heat stress might have been a factor in precipitating a clinical attack of an infection previously acquired in the endemic zone. Attention is drawn to the importance of delayed attacks of P. vivax and, in semi-immunes, of P. falciparum. The time interval involved in establishing a history of "recent" travel in clinically suspected cases of malaria needs to be more clearly defined in each geographical area. Cases of induced malaria due to transfusion, accidental and congenital infections were identified. The fatality rate due to P. falciparum infections was low. In terms of the risk of renewed transmission, Kuwait may be considered a vulnerable area.

  1. Transmission

    SciTech Connect

    Sugano, K.

    1988-12-27

    A transmission is described which consists of: an input shaft; an output shaft; a first planetary gear set including a first sun gear selectively connectable by a first clutch to the input shaft, a first carrier selectively connectable by a second clutch to the input shaft and a first ring gear connected to the output shaft. The first sun gear selectively held stationary by a first brake, the first carrier is allowed to rotate in the same forward direction as the input shaft when the second clutch is engaged, but prevented from rotating in a reverse direction opposite to the forward direction by a first one-way clutch, the first carrier being selectively held stationary by a second brake; a second planetary gear set including a second sun gear connected to the input shaft, a second carrier connected to the first ring gear and also the the output shaft, and a second ring gear.

  2. Malaria Treatment (United States)

    MedlinePlus

    ... Malaria Branch clinician. malaria@cdc.gov Malaria Treatment (United States) Recommend on Facebook Tweet Share Compartir Treatment of Malaria: Guidelines For Clinicians (United States) Download PDF version of Parts 1-3 formatted ...

  3. Malaria Pathogenesis

    NASA Astrophysics Data System (ADS)

    Miller, Louis H.; Good, Michael F.; Milon, Genevieve

    1994-06-01

    Malaria is a disease caused by repeated cycles of growth of the parasite Plasmodium in the erythrocyte. Various cellular and molecular strategies allow the parasite to evade the human immune response for many cycles of parasite multiplication. Under certain circumstances Plasmodium infection causes severe anemia or cerebral malaria; the expression of disease is influenced by both parasite and host factors, as exemplified by the exacerbation of disease during pregnancy. This article provides an overview of malaria pathogenesis, synthesizing the recent field, laboratory, and epidemiological data that will lead to the development of strategies to reduce mortality and morbidity.

  4. Ongoing challenges in the management of malaria

    PubMed Central

    Kokwaro, Gilbert

    2009-01-01

    This article gives an overview of some of the ongoing challenges that are faced in the prevention, diagnosis and treatment of malaria. Malaria causes approximately 881,000 deaths every year, with nine out of ten deaths occurring in sub-Saharan Africa. In addition to the human burden of malaria, the economic burden is vast. It is thought to cost African countries more than US$12 billion every year in direct losses. However, great progress in malaria control has been made in some highly endemic countries. Vector control is assuming a new importance with the significant reductions in malaria burden achieved using combined malaria control interventions in countries such as Zanzibar, Zambia and Rwanda. The proportion of patients treated for malaria who have a confirmed diagnosis is low in Africa compared with other regions of the world, with the result that anti-malarials could be used to treat patients without malaria, especially in areas where progress has been made in reducing the malaria burden and malaria epidemiology is changing. Inappropriate administration of anti-malarials could contribute to the spread of resistance and incurs unnecessary costs. Parasite resistance to almost all commonly used anti-malarials has been observed in the most lethal parasite species, Plasmodium falciparum. This has presented a major barrier to successful disease management in malaria-endemic areas. ACT (artemisinin-based combination therapy) has made a significant contribution to malaria control and to reducing disease transmission through reducing gametocyte carriage. Administering ACT to infants and small children can be difficult and time consuming. Specially formulating anti-malarials for this vulnerable population is vital to ease administration and help ensure that an accurate dose is received. Education of healthworkers and communities about malaria prevention, diagnosis and treatment is a vital component of effective case management, especially as diagnostic policies change

  5. Malaria successes and challenges in Asia.

    PubMed

    Bhatia, Rajesh; Rastogi, Rakesh Mani; Ortega, Leonard

    2013-12-01

    Asia ranks second to Africa in terms of malaria burden. In 19 countries of Asia, malaria is endemic and 2.31 billion people or 62% of the total population in these countries are at risk of malaria. In 2010, WHO estimated around 34.8 million cases and 45,600 deaths due to malaria in Asia. In 2011, 2.7 million cases and > 2000 deaths were reported. India, Indonesia, Myanmar and Pakistan are responsible for >85% of the reported cases (confirmed) and deaths in Asia. In last 10 yr, due to availability of donor's fund specially from Global fund, significant progress has been made by the countries in Asia in scaling-up malaria control interventions which were instrumental in reducing malaria morbidity and mortality significantly. There is a large heterogeneity in malaria epidemiology in Asia. As a result, the success in malaria control/elimination is also diverse. As compared to the data of the year 2000, out of 19 malaria endemic countries, 12 countries were able to reduce malaria incidence (microscopically confirmed cases only) by 75%. Two countries, namely Bangladesh and Malaysia are projected to reach 75% reduction by 2015 while India is projected to reach 50-75% only by 2015. The trend could not be assessed in four countries, namely Indonesia, Myanmar, Pakistan and Timor-Leste due to insufficient consistent data. Numerous key challenges need to be addressed to sustain the gains and eliminate malaria in most parts of Asia. Some of these are to control the spread of resistance in Plasmodium falciparum to artemisinin, control of outdoor transmission, control of vivax malaria and ensuring universal coverage of key interventions. Asia has the potential to influence the malaria epidemiology all over the world as well as to support the global efforts in controlling and eliminating malaria through production of quality-assured ACTs, RDTs and long-lasting insecticidal nets.

  6. Climate change unlikely to increase malaria burden in West Africa

    NASA Astrophysics Data System (ADS)

    Yamana, Teresa K.; Bomblies, Arne; Eltahir, Elfatih A. B.

    2016-11-01

    The impact of climate change on malaria transmission has been hotly debated. Recent conclusions have been drawn using relatively simple biological models and statistical approaches, with inconsistent predictions. Consequently, the Intergovernmental Panel on Climate Change Fifth Assessment Report (IPCC AR5) echoes this uncertainty, with no clear guidance for the impacts of climate change on malaria transmission, yet recognizing a strong association between local climate and malaria. Here, we present results from a decade-long study involving field observations and a sophisticated model simulating village-scale transmission. We drive the malaria model using select climate models that correctly reproduce historical West African climate, and project reduced malaria burden in a western sub-region and insignificant impact in an eastern sub-region. Projected impacts of climate change on malaria transmission in this region are not of serious concern.

  7. Malaria vaccine.

    PubMed

    1994-05-01

    Some have argued that the vaccine against malaria developed by Manuel Pattaroyo, a Colombian scientist, is being tested prematurely in humans and that it is unlikely to be successful. While the Pattaroyo vaccine has been shown to confer protection against the relatively mild malaria found in Colombia, doubts exist over whether it will be effective in Africa. Encouraging first results, however, are emerging from field tests in Tanzania. The vaccine triggered a strong new immune response, even in individuals previously exposed to malaria. Additional steps must be taken to establish its impact upon mortality and morbidity. Five major trials are underway around the world. The creator estimates that the first ever effective malaria vaccine could be available for widespread use within five years and he has no intention of securing a patent for the discovery. In another development, malaria specialists from 35 African countries convened at an international workshop in Zimbabwe to compare notes. Participants disparaged financial outlays for the fight against malaria equivalent to 2% of total AIDS funding as insufficient; noted intercountry differences in prevention, diagnosis, and treatment; and found information exchange between anglophone and francophone doctors to be generally poor.

  8. Unravelling the relationships between Anopheles darlingi (Diptera: Culicidae) densities, environmental factors and malaria incidence: understanding the variable patterns of malarial transmission in French Guiana (South America)

    PubMed Central

    Girod, R; Roux, E; Berger, F; Stefani, A; GAborit, P; Carinci, R; Issaly, J; Carme, B; Dusfour, I

    2011-01-01

    Anopheles darlingi, one of the main malaria vectors in the Neotropics, is widely distributed in French Guiana, where malaria remains a major public-health problem. Elucidation of the relationships between the population dynamics of An. darlingi and local environmental factors would appear to be an essential factor in the epidemiology of human malaria in French Guiana and the design of effective vector-control strategies. In a recent investigation, longitudinal entomological surveys were carried out for 2–4 years in one village in each of three distinct endemic areas of French Guiana. Anopheles darlingi was always the anopheline mosquito that was most frequently caught on human bait, although its relative abundance (as a proportion of all the anophelines collected) and human biting rate (in bites/person-year) differed with the study site. Seasonality in the abundance of human-landing An. darlingi (with peaks at the end of the rainy season) was observed in only two of the three study sites. Just three An. darlingi were found positive for Plasmodium (either P. falciparum or P. vivax) circumsporozoite protein, giving entomological inoculation rates of 0·0–8·7 infectious bites/person-year. Curiously, no infected An. darlingi were collected in the village with the highest incidence of human malaria. Relationships between malaria incidence, An. darlingi densities, rainfall and water levels in the nearest rivers were found to be variable and apparently dependent on land-cover specificities that reflected the diversity and availability of habitats suitable for the development and reproduction of An. darlingi. PMID:21396247

  9. A simple method for defining malaria seasonality

    PubMed Central

    2009-01-01

    Background There is currently no standard way of defining malaria seasonality, resulting in a wide range of definitions reported in the literature. Malaria cases show seasonal peaks in most endemic settings, and the choice and timing for optimal malaria control may vary by seasonality. A simple approach is presented to describe the seasonality of malaria, to aid localized policymaking and targeting of interventions. Methods A series of systematic literature reviews were undertaken to identify studies reporting on monthly data for full calendar years on clinical malaria, hospital admission with malaria and entomological inoculation rates (EIR). Sites were defined as having 'marked seasonality' if 75% or more of all episodes occurred in six or less months of the year. A 'concentrated period of malaria' was defined as the six consecutive months with the highest cumulative proportion of cases. A sensitivity analysis was performed based on a variety of cut-offs. Results Monthly data for full calendar years on clinical malaria, all hospital admissions with malaria, and entomological inoculation rates were available for 13, 18, and 11 sites respectively. Most sites showed year-round transmission with seasonal peaks for both clinical malaria and hospital admissions with malaria, with a few sites fitting the definition of 'marked seasonality'. For these sites, consistent results were observed when more than one outcome or more than one calendar year was available from the same site. The use of monthly EIR data was found to be of limited value when looking at seasonal variations of malaria transmission, particularly at low and medium intensity levels. Conclusion The proposed definition discriminated well between studies with 'marked seasonality' and those with less seasonality. However, a poor fit was observed in sites with two seasonal peaks. Further work is needed to explore the applicability of this definition on a wide-scale, using routine health information system data

  10. A Research Agenda for Malaria Eradication: Drugs

    PubMed Central

    2011-01-01

    Antimalarial drugs will be essential tools at all stages of malaria elimination along the path towards eradication, including the early control or “attack” phase to drive down transmission and the later stages of maintaining interruption of transmission, preventing reintroduction of malaria, and eliminating the last residual foci of infection. Drugs will continue to be used to treat acute malaria illness and prevent complications in vulnerable groups, but better drugs are needed for elimination-specific indications such as mass treatment, curing asymptomatic infections, curing relapsing liver stages, and preventing transmission. The ideal malaria eradication drug is a coformulated drug combination suitable for mass administration that can be administered in a single encounter at infrequent intervals and that results in radical cure of all life cycle stages of all five malaria species infecting humans. Short of this optimal goal, highly desirable drugs might have limitations such as targeting only one or two parasite species, the priorities being Plasmodium falciparum and Plasmodium vivax. The malaria research agenda for eradication should include research aimed at developing such drugs and research to develop situation-specific strategies for using both current and future drugs to interrupt malaria transmission. PMID:21311580

  11. Malaria in Pregnancy

    PubMed Central

    Takem, Ebako Ndip; D’Alessandro, Umberto

    2013-01-01

    Pregnant women have a higher risk of malaria compared to non-pregnant women. This review provides an update on knowledge acquired since 2000 on P. falciparum and P.vivax infections in pregnancy. Maternal risk factors for malaria in pregnancy (MiP) include low maternal age, low parity, and low gestational age. The main effects of MIP include maternal anaemia, low birth weight (LBW), preterm delivery and increased infant and maternal mortality. P. falciparum infected erythrocytes sequester in the placenta by expressing surface antigens, mainly variant surface antigen (VAR2CSA), that bind to specific receptors, mainly chondroitin sulphate A. In stable transmission settings, the higher malaria risk in primigravidae can be explained by the non-recognition of these surface antigens by the immune system. Recently, placental sequestration has been described also for P.vivax infections. The mechanism of preterm delivery and intrauterine growth retardation is not completely understood, but fever (preterm delivery), anaemia, and high cytokines levels have been implicated. Clinical suspicion of MiP should be confirmed by parasitological diagnosis. The sensitivity of microscopy, with placenta histology as the gold standard, is 60% and 45% for peripheral and placental falciparum infections in African women, respectively. Compared to microscopy, RDTs have a lower sensitivity though when the quality of microscopy is low RDTs may be more reliable. Insecticide treated nets (ITN) and intermittent preventive treatment in pregnancy (IPTp) are recommended for the prevention of MiP in stable transmission settings. ITNs have been shown to reduce malaria infection and adverse pregnancy outcomes by 28–47%. Although resistance is a concern, SP has been shown to be equivalent to MQ and AQ for IPTp. For the treatment of uncomplicated malaria during the first trimester, quinine plus clindamycin for 7 days is the first line treatment and artesunate plus clindamycin for 7 days is indicated if

  12. The Plasmodium falciparum Cell-Traversal Protein for Ookinetes and Sporozoites as a Candidate for Preerythrocytic and Transmission-Blocking Vaccines

    PubMed Central

    Espinosa, Diego A.; Vega-Rodriguez, Joel; Flores-Garcia, Yevel; Noe, Amy R.; Muñoz, Christian; Coleman, Russell; Bruck, Torben; Haney, Keith; Stevens, Alex; Retallack, Diane; Allen, Jeff; Vedvick, Thomas S.; Fox, Christopher B.; Reed, Steven G.; Howard, Randall F.; Salman, Ahmed M.; Janse, Chris J.; Khan, Shahid M.

    2016-01-01

    ABSTRACT Recent studies have shown that immune responses against the cell-traversal protein for Plasmodium ookinetes and sporozoites (CelTOS) can inhibit parasite infection. While these studies provide important evidence toward the development of vaccines targeting this protein, it remains unknown whether these responses could engage the Plasmodium falciparum CelTOS in vivo. Using a newly developed rodent malaria chimeric parasite expressing the P. falciparum CelTOS (PfCelTOS), we evaluated the protective effect of in vivo immune responses elicited by vaccination and assessed the neutralizing capacity of monoclonal antibodies specific against PfCelTOS. Mice immunized with recombinant P. falciparum CelTOS in combination with the glucopyranosyl lipid adjuvant-stable emulsion (GLA-SE) or glucopyranosyl lipid adjuvant-liposome-QS21 (GLA-LSQ) adjuvant system significantly inhibited sporozoite hepatocyte infection. Notably, monoclonal antibodies against PfCelTOS strongly inhibited oocyst development of P. falciparum and Plasmodium berghei expressing PfCelTOS in Anopheles gambiae mosquitoes. Taken together, our results demonstrate that anti-CelTOS responses elicited by vaccination or passive immunization can inhibit sporozoite and ookinete infection and impair vector transmission. PMID:27895131

  13. Biosignatures of Exposure/Transmission and Immunity.

    PubMed

    King, Christopher L; Davies, D Huw; Felgner, Phil; Baum, Elizabeth; Jain, Aarti; Randall, Arlo; Tetteh, Kevin; Drakeley, Christopher J; Greenhouse, Bryan

    2015-09-01

    A blood test that captures cumulative exposure over time and assesses levels of naturally acquired immunity (NAI) would provide a critical tool to monitor the impact of interventions to reduce malaria transmission and broaden our understanding of how NAI develops around the world as a function of age and exposure. This article describes a collaborative effort in multiple International Centers of Excellence in Malaria Research (ICEMRs) to develop such tests using malaria-specific antibody responses as biosignatures of transmission and immunity. The focus is on the use of Plasmodium falciparum and Plasmodium vivax protein microarrays to identify a panel of the most informative antibody responses in diverse malaria-endemic settings representing an unparalleled spectrum of malaria transmission and malaria species mixes before and after interventions to reduce malaria transmission.

  14. Plasmodium knowlesi malaria in children.

    PubMed

    Barber, Bridget E; William, Timothy; Jikal, Mohammad; Jilip, Jenarun; Dhararaj, Prabakaran; Menon, Jayaram; Yeo, Tsin W; Anstey, Nicholas M

    2011-05-01

    Plasmodium knowlesi can cause severe malaria in adults; however, descriptions of clinical disease in children are lacking. We reviewed case records of children (age <15 years) with a malaria diagnosis at Kudat District Hospital, serving a largely deforested area of Sabah, Malaysia, during January-November 2009. Sixteen children with PCR-confirmed P. knowlesi monoinfection were compared with 14 children with P. falciparum monoinfection diagnosed by microscopy or PCR. Four children with knowlesi malaria had a hemoglobin level at admission of <10.0 g/dL (minimum lowest level 6.4 g/dL). Minimum level platelet counts were lower in knowlesi than in falciparum malaria (median 76,500/μL vs. 156,000/mL; p = 0.01). Most (81%) children with P. knowlesi malaria received chloroquine and primaquine; median parasite clearance time was 2 days (range 1-5 days). P. knowlesi is the most common cause of childhood malaria in Kudat. Although infection is generally uncomplicated, anemia is common and thrombocytopenia universal. Transmission dynamics in this region require additional investigation.

  15. Plasmodium falciparum GFP-E-NTPDase expression at the intraerythrocytic stages and its inhibition blocks the development of the human malaria parasite.

    PubMed

    Borges-Pereira, Lucas; Meissner, Kamila Anna; Wrenger, Carsten; Garcia, Célia R S

    2017-03-11

    Plasmodium falciparum is the causative agent of the most dangerous form of malaria in humans. It has been reported that the P. falciparum genome encodes for a single ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase), an enzyme that hydrolyzes extracellular tri- and di-phosphate nucleotides. The E-NTPDases are known for participating in invasion and as a virulence factor in many pathogenic protozoa. Despite its presence in the parasite genome, currently, no information exists about the activity of this predicted protein. Here, we show for the first time that P. falciparum E-NTPDase is relevant for parasite lifecycle as inhibition of this enzyme impairs the development of P. falciparum within red blood cells (RBCs). ATPase activity could be detected in rings, trophozoites, and schizonts, as well as qRT-PCR, confirming that E-NTPDase is expressed throughout the intraerythrocytic cycle. In addition, transfection of a construct which expresses approximately the first 500 bp of an E-NTPDase-GFP chimera shows that E-NTPDase co-localizes with the endoplasmic reticulum (ER) in the early stages and with the digestive vacuole (DV) in the late stages of P. falciparum intraerythrocytic cycle.

  16. Luciferase-Based, High-Throughput Assay for Screening and Profiling Transmission-Blocking Compounds against Plasmodium falciparum Gametocytes

    PubMed Central

    Lucantoni, Leonardo; Fidock, David A.

    2016-01-01

    The discovery of new antimalarial drugs able to target both the asexual and gametocyte stages of Plasmodium falciparum is critical to the success of the malaria eradication campaign. We have developed and validated a robust, rapid, and cost-effective high-throughput reporter gene assay to identify compounds active against late-stage (stage IV and V) gametocytes. The assay, which is suitable for testing compound activity at incubation times up to 72 h, demonstrates excellent quality and reproducibility, with average Z′ values of 0.85 ± 0.01. We used the assay to screen more than 10,000 compounds from three chemically diverse libraries. The screening outcomes highlighted the opportunity to use collections of compounds with known activity against the asexual stages of the parasites as a starting point for gametocytocidal activity detection in order to maximize the chances of identifying gametocytocidal compounds. This assay extends the capabilities of our previously reported luciferase assay, which tested compounds against early-stage gametocytes, and opens possibilities to profile the activities of gametocytocidal compounds over the entire course of gametocytogenesis. PMID:26787698

  17. Malaria Modeling and Surveillance for the Greater Mekong Subregion

    NASA Technical Reports Server (NTRS)

    Kiang, Richard; Adimi, Farida; Soika, Valerii; Nigro, Joseph

    2005-01-01

    At 4,200 km, the Mekong River is the tenth longest river in the world. It directly and indirectly influences the lives of hundreds of millions of inhabitants in its basin. The riparian countries - Thailand, Myanmar, Cambodia, Laos, Vietnam, and a small part of China - form the Greater Mekong Subregion (GMS). This geographical region has the misfortune of being the world's epicenter of falciparum malaria, which is the most severe form of malaria caused by Plasmodium falciparum. Depending on the country, approximately 50 to 90% of all malaria cases are due to this species. In the Malaria Modeling and Surveillance Project, we have been developing techniques to enhance public health's decision capability for malaria risk assessments and controls. The main objectives are: 1) Identifying the potential breeding sites for major vector species; 2) Implementing a malaria transmission model to identify the key factors that sustain or intensify malaria transmission; and 3) Implementing a risk algorithm to predict the occurrence of malaria and its transmission intensity. The potential benefits are: 1) Increased warning time for public health organizations to respond to malaria outbreaks; 2) Optimized utilization of pesticide and chemoprophylaxis; 3) Reduced likelihood of pesticide and drug resistance; and 4) Reduced damage to environment. Environmental parameters important to malaria transmission include temperature, relative humidity, precipitation, and vegetation conditions. These parameters are extracted from NASA Earth science data sets. Hindcastings based on these environmental parameters have shown good agreement to epidemiological records.

  18. [The epidemic situation with malaria in Turkmenistan].

    PubMed

    Amangel'diev, K A; Morozova, K V; Medalieva, D O

    2000-01-01

    As a result of comprehensive research on the causative agents and vectors of malaria and wide use of synthetic antimalarials and highly effective residual insecticides, endemic malaria was eliminated in Turkmenistan by 1960. During the period 1965-1980, 23 local cases of malaria were recorded in Turkmenistan. These local cases were confined to the regions of Mary and Akhal, on the borders of neighbouring countries. In 1998 the epidemiological situation in the country worsened and local transmission of infection resumed. During the year the number of cases recorded was 137:134 being a first diagnosis of the disease and three being relapsed cases. In comparison with 1997, the previous year, incidence was up by 123 cases (a 9.7-fold increase), while the incidence of imported cases of malaria went up by 11 (a 2.2-fold increase), principally in Dashkhovuz and Lebar regions, being brought in from malaria foci in Gushgin district, Turkey, Azerbaijan and Tadjikistan. Local transmission of malaria went up by 111 cases (a 27.7 fold increase); 108 cases were recorded in Gushgin district, Mary region. The first case of malaria in Gushkin district was detected in June 1998. At that time there were five active foci. The approximate number of inhabitants in the active focus area was 10,000. The appearance of local malaria in border districts was caused by the periodic influx of infected mosquitos from neighbouring countries (Afghanistan).

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

    PubMed Central

    Bousema, Teun; Drakeley, Chris

    2011-01-01

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

  20. Transmission of malaria in relation to distribution and coverage of long-lasting insecticidal nets in central Côte d’Ivoire

    PubMed Central

    2014-01-01

    Background The use of long-lasting insecticidal nets (LLINs) is an effective malaria control strategy. However, there are challenges to achieve high coverage, such as distribution sustainability, and coverage keep-up. This study assessed the effect of LLINs coverage and contextual factors on entomological indicators of malaria in rural Côte d’Ivoire. Methods The study was carried out between July 2009 and May 2012 in three villages (Bozi, N’Dakonankro and Yoho) of central Côte d’Ivoire. In Bozi and Yoho, LLINs were distributed free of charge by the national malaria control programme in 2008. In Bozi, an additional distribution was carried out in May 2011. No specific interventions were done in N’Dakonankro. Entomological surveys were conducted in July 2009 and July 2010 (baseline), and in August and November 2011 and in February 2012. Frequency of circumsporozoite protein was determined using an enzyme-linked immunosorbent assay. Regression models were employed to assess the impact of LLINs and changing patterns of irrigated rice farming on entomological parameters, and to determine associations with LLINs coverage and other contextual factors. Results In Bozi, high proportion of LLIN usage was observed (95-100%). After six months, 95% of LLINs were washed at least once and 79% were washed up to three times within one year. Anopheles gambiae was the predominant malaria vector (66.6% of all mosquitoes caught). From 2009 to 2012, in N’Dakonankro, the mean annual entomological inoculation rate (EIR) increased significantly from 116.8 infectious bites/human/year (ib/h/y) to 408.8 ib/h/y, while in the intervention villages, the EIR decreased significantly from 514.6 ib/h/y to 62.0 ib/h/y (Bozi) and from 83.9 ib/h/y to 25.5 ib/h/y (Yoho). The risk of an infectious bite over the three-year period was significantly lower in the intervention villages compared to the control village (p <0.001). Conclusion High coverage and sensitization of households to use

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

    NASA Astrophysics Data System (ADS)

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

    2013-12-01

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

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

    PubMed

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

    2013-12-12

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

  3. Modeling the impact on virus transmission of Wolbachia-mediated blocking of dengue virus infection of Aedes aegypti.

    PubMed

    Ferguson, Neil M; Kien, Duong Thi Hue; Clapham, Hannah; Aguas, Ricardo; Trung, Vu Tuan; Chau, Tran Nguyen Bich; Popovici, Jean; Ryan, Peter A; O'Neill, Scott L; McGraw, Elizabeth A; Long, Vo Thi; Dui, Le Thi; Nguyen, Hoa L; Chau, Nguyen Van Vinh; Wills, Bridget; Simmons, Cameron P

    2015-03-18

    Dengue is the most common arboviral infection of humans and is a public health burden in more than 100 countries. Aedes aegypti mosquitoes stably infected with strains of the intracellular bacterium Wolbachia are resistant to dengue virus (DENV) infection and are being tested in field trials. To mimic field conditions, we experimentally assessed the vector competence of A. aegypti carrying the Wolbachia strains wMel and wMelPop after challenge with viremic blood from dengue patients. We found that wMelPop conferred strong resistance to DENV infection of mosquito abdomen tissue and largely prevented disseminated infection. wMel conferred less resistance to infection of mosquito abdomen tissue, but it did reduce the prevalence of mosquitoes with infectious saliva. A mathematical model of DENV transmission incorporating the dynamics of viral infection in humans and mosquitoes was fitted to the data collected. Model predictions suggested that wMel would reduce the basic reproduction number, R0, of DENV transmission by 66 to 75%. Our results suggest that establishment of wMelPop-infected A. aegypti at a high frequency in a dengue-endemic setting would result in the complete abatement of DENV transmission. Establishment of wMel-infected A. aegypti is also predicted to have a substantial effect on transmission that would be sufficient to eliminate dengue in low or moderate transmission settings but may be insufficient to achieve complete control in settings where R0 is high. These findings develop a framework for selecting Wolbachia strains for field releases and for calculating their likely impact.

  4. Functional evaluation of malaria Pfs25 DNA vaccine by in vivo electroporation in olive baboons.

    PubMed

    Kumar, Rajesh; Nyakundi, Ruth; Kariuki, Thomas; Ozwara, Hastings; Nyamongo, Onkoba; Mlambo, Godfree; Ellefsen, Barry; Hannaman, Drew; Kumar, Nirbhay

    2013-06-28

    Plasmodium falciparum Pfs25 antigen, expressed on the surface of zygotes and ookinetes, is one of the leading targets for the development of a malaria transmission-blocking vaccine (TBV). Our laboratory has been evaluating DNA plasmid based Pfs25 vaccine in mice and non-human primates. Previously, we established that in vivo electroporation (EP) delivery is an effective method to improve the immunogenicity of DNA vaccine encoding Pfs25 in mice. In order to optimize the in vivo EP procedure and test for its efficacy in more clinically relevant larger animal models, we employed in vivo EP to evaluate the immune response and protective efficacy of Pfs25 encoding DNA vaccine in nonhuman primates (olive baboons, Papio anubis). The results showed that at a dose of 2.5mg DNA vaccine, antibody responses were significantly enhanced with EP as compared to without EP resulting in effective transmission blocking efficiency. Similar immunogenicity enhancing effect of EP was also observed with lower doses (0.5mg and 1mg) of DNA plasmids. Further, final boosting with a single dose of recombinant Pfs25 protein resulted in dramatically enhanced antibody titers and significantly increased functional transmission blocking efficiency. Our study suggests priming with DNA vaccine via EP along with protein boost regimen as an effective method to elicit potent immunogenicity of malaria DNA vaccines in nonhuman primates and provides the basis for further evaluation in human volunteers.

  5. Timeliness of Malaria Surveillance System in Iran

    PubMed Central

    AKBARI, Hossein; MAJDZADEH, Reza; RAHIMI FOROUSHANI, Abbas; RAEISI, Ahmad

    2013-01-01

    Background: We aimed to evaluate the timeliness of reporting of malaria surveillance system and understanding the existing problems. Methods: The timeliness of malaria surveillance system of Iran was evaluated in four provinces of Iran including Sistan & Baluchistan, Hormozgan, Kerman (as provinces with local malaria transmission) and Khuzestan (without local malaria transmission). In this descriptive-analytic cross-sectional study two levels of Primary Health Care service providers including first level (Health Houses) and second level (Urban or Rural Health care units) were evaluated with regard to reporting of malaria surveillance system. Results: Forms number 1 (87% reported within one day) and number 2 (reporting median: 2 days) are reported from first level to second level, and forms number 4 (median: 4 days), number 3 (median: 6 days), number 7 (median: 9 days), number 5 (median: 11 days) and number 6 (median: 19 days) are reported from second level to the third level respectively in a shorter time. Independent variables such as distance, local malaria transmission level, and case finding type, are the factors affecting the reporting delay. Conclusion: Reporting in the first level compared to the second level is done with lower delay. In the areas where there is a deadline set for reporting, reporting is done more timely. Whatever number of malaria cases is decreased, sensitivity and subsequently timeliness reduced. It is recommended that the studies of timeliness be done with sensitivity and usefulness analysis of surveillance system. PMID:23515191

  6. Epidemiology of Plasmodium vivax Malaria in Peru.

    PubMed

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

    2016-12-28

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

  7. Epidemiology of Plasmodium vivax Malaria in Peru

    PubMed Central

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

    2016-01-01

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

  8. Low autochtonous urban malaria in Antananarivo (Madagascar)

    PubMed Central

    Rabarijaona, Léon Paul; Ariey, Frédéric; Matra, Robert; Cot, Sylvie; Raharimalala, Andrianavalona Lucie; Ranaivo, Louise Henriette; Le Bras, Jacques; Robert, Vincent; Randrianarivelojosia, Milijaona

    2006-01-01

    Background The study of urban malaria is an area undergoing rapid expansion, after many years of neglect. The problem of over-diagnosis of malaria, especially in low transmission settings including urban areas, is also receiving deserved attention. The primary objective of the present study was to assess the frequency of malaria among febrile outpatients seen in private and public primary care facilities of Antananarivo. The second aim was to determine, among the diagnosed malaria cases, the contribution of autochthonous urban malaria. Methods Two cross-sectional surveys in 43 health centres in Antananarivo in February 2003 (rainy season) and in July 2003 (dry season) were conducted. Consenting clinically suspected malaria patients with fever or history of fever in the past 48 hours were included. Malaria rapid diagnostic tests and microscopy were used to diagnose malaria. Basic information was collected from patients to try to identify the origin of the infection: autochthonous or introduced. Results In February, among 771 patients, 15 (1.9%) positive cases were detected. Three malaria parasites were implicated: Plasmodium. falciparum (n = 12), Plasmodium vivax (n = 2) and Plasmodium. ovale (n = 1). Only two cases, both P. falciparum, were likely to have been autochthonous (0.26%). In July, among 739 blood smears examined, 11 (1.5%) were positive: P. falciparum (n = 9) and P. vivax (n = 2). Three cases of P. falciparum malaria were considered to be of local origin (0.4%). Conclusion This study demonstrates that malaria cases among febrile episodes are low in Antananarivo and autochthonous malaria cases exist but are rare. PMID:16573843

  9. Biodiversity Can Help Prevent Malaria Outbreaks in Tropical Forests

    PubMed Central

    Laporta, Gabriel Zorello; de Prado, Paulo Inácio Knegt Lopez; Kraenkel, Roberto André; Coutinho, Renato Mendes; Sallum, Maria Anice Mureb

    2013-01-01

    Background Plasmodium vivax is a widely distributed, neglected parasite that can cause malaria and death in tropical areas. It is associated with an estimated 80–300 million cases of malaria worldwide. Brazilian tropical rain forests encompass host- and vector-rich communities, in which two hypothetical mechanisms could play a role in the dynamics of malaria transmission. The first mechanism is the dilution effect caused by presence of wild warm-blooded animals, which can act as dead-end hosts to Plasmodium parasites. The second is diffuse mosquito vector competition, in which vector and non-vector mosquito species compete for blood feeding upon a defensive host. Considering that the World Health Organization Malaria Eradication Research Agenda calls for novel strategies to eliminate malaria transmission locally, we used mathematical modeling to assess those two mechanisms in a pristine tropical rain forest, where the primary vector is present but malaria is absent. Methodology/Principal Findings The Ross–Macdonald model and a biodiversity-oriented model were parameterized using newly collected data and data from the literature. The basic reproduction number () estimated employing Ross–Macdonald model indicated that malaria cases occur in the study location. However, no malaria cases have been reported since 1980. In contrast, the biodiversity-oriented model corroborated the absence of malaria transmission. In addition, the diffuse competition mechanism was negatively correlated with the risk of malaria transmission, which suggests a protective effect provided by the forest ecosystem. There is a non-linear, unimodal correlation between the mechanism of dead-end transmission of parasites and the risk of malaria transmission, suggesting a protective effect only under certain circumstances (e.g., a high abundance of wild warm-blooded animals). Conclusions/Significance To achieve biological conservation and to eliminate Plasmodium parasites in human populations

  10. Mitochondrial ATP synthase is dispensable in blood-stage Plasmodium berghei rodent malaria but essential in the mosquito phase

    PubMed Central

    Sturm, Angelika; Mollard, Vanessa; Cozijnsen, Anton; Goodman, Christopher D.; McFadden, Geoffrey I.

    2015-01-01

    Mitochondrial ATP synthase is driven by chemiosmotic oxidation of pyruvate derived from glycolysis. Blood-stage malaria parasites eschew chemiosmosis, instead relying almost solely on glycolysis for their ATP generation, which begs the question of whether mitochondrial ATP synthase is necessary during the blood stage of the parasite life cycle. We knocked out the mitochondrial ATP synthase β subunit gene in the rodent malaria parasite, Plasmodium berghei, ablating the protein that converts ADP to ATP. Disruption of the β subunit gene of the ATP synthase only marginally reduced asexual blood-stage parasite growth but completely blocked mouse-to-mouse transmission via Anopheles stephensi mosquitoes. Parasites lacking the β subunit gene of the ATP synthase generated viable gametes that fuse and form ookinetes but cannot progress beyond this stage. Ookinetes lacking the β subunit gene of the ATP synthase had normal motility but were not viable in the mosquito midgut and never made oocysts or sporozoites, thereby abrogating transmission to naive mice via mosquito bite. We crossed the self-infertile ATP synthase β subunit knockout parasites with a male-deficient, self-infertile strain of P. berghei, which restored fertility and production of oocysts and sporozoites, which demonstrates that mitochondrial ATP synthase is essential for ongoing viability through the female, mitochondrion-carrying line of sexual reproduction in P. berghei malaria. Perturbation of ATP synthase completely blocks transmission to the mosquito vector and could potentially be targeted for disease control. PMID:25831536

  11. Treatment-seeking behaviour for malaria in children under five years of age: implication for home management in rural areas with high seasonal transmission in Sudan

    PubMed Central

    Malik, Elfatih Mohamed; Hanafi, Kamal; Ali, Salah Hussein; Ahmed, Eldirdieri Salim; Mohamed, Khalid Awad

    2006-01-01

    Background Effective management of malaria in children under the age of 5 requires mothers to seek, obtain, and use medication appropriately. This is linked to timely decision, accessibility, correct use of the drugs and follow-up. The aim of the study is to identify the basis on which fever was recognized and classified and exploring factors involved in selection of different treatment options. Methods Data was obtained by interviewing 96 mothers who had brought their febrile children to selected health facilities, conduction of 10 focus group discussions with mothers at village level as well as by observation. Results A high score of mothers' knowledge and recognition of fever/malaria was recorded. Mothers usually start care at home and, within an average of three days, they shift to health workers if there was no response. The main health-seeking behaviour is to consult the nearest health facility or health personnel together with using traditional medicine or herbs. There are also health workers who visit patients at home. The majority of mothers with febrile children reported taking drugs before visiting a health facility. The choice between the available options determined by the availability of health facilities, user fees, satisfaction with services, difficulty to reach the facilities and believe in traditional medicine. Conclusion Mothers usually go through different treatment option before consulting health facilities ending with obvious delay in seeking care. As early effective treatment is the main theme of the control programme, implementation of malaria home management strategy is urgently needed to improve the ongoing practice. PMID:16859565

  12. High Rates of Asymptomatic, Sub-microscopic Plasmodium vivax Infection and Disappearing Plasmodium falciparum Malaria in an Area of Low Transmission in Solomon Islands

    PubMed Central

    Waltmann, Andreea; Darcy, Andrew W.; Harris, Ivor; Koepfli, Cristian; Lodo, John; Vahi, Ventis; Piziki, David; Shanks, G. Dennis; Barry, Alyssa E.; Whittaker, Maxine; Kazura, James W.; Mueller, Ivo

    2015-01-01

    Introduction Solomon Islands is intensifying national efforts to achieve malaria elimination. A long history of indoor spraying with residual insecticides, combined recently with distribution of long lasting insecticidal nets and artemether-lumefantrine therapy, has been implemented in Solomon Islands. The impact of these interventions on local endemicity of Plasmodium spp. is unknown. Methods In 2012, a cross-sectional survey of 3501 residents of all ages was conducted in Ngella, Central Islands Province, Solomon Islands. Prevalence of Plasmodium falciparum, P. vivax, P. ovale and P. malariae was assessed by quantitative PCR (qPCR) and light microscopy (LM). Presence of gametocytes was determined by reverse transcription quantitative PCR (RT-qPCR). Results By qPCR, 468 Plasmodium spp. infections were detected (prevalence = 13.4%; 463 P. vivax, five mixed P. falciparum/P. vivax, no P. ovale or P. malariae) versus 130 by LM (prevalence = 3.7%; 126 P. vivax, three P. falciparum and one P. falciparum/P. vivax). The prevalence of P. vivax infection varied significantly among villages (range 3.0–38.5%, p<0.001) and across age groups (5.3–25.9%, p<0.001). Of 468 P. vivax infections, 72.9% were sub-microscopic, 84.5% afebrile and 60.0% were both sub-microscopic and afebrile. Local residency, low education level of the household head and living in a household with at least one other P. vivax infected individual increased the risk of P. vivax infection. Overall, 23.5% of P. vivax infections had concurrent gametocytaemia. Of all P. vivax positive samples, 29.2% were polyclonal by MS16 and msp1F3 genotyping. All five P. falciparum infections were detected in residents of the same village, carried the same msp2 allele and four were positive for P. falciparum gametocytes. Conclusion P. vivax infection remains endemic in Ngella, with the majority of cases afebrile and below the detection limit of LM. P. falciparum has nearly disappeared, but the risk of re-introductions and

  13. Cerebral Malaria.

    PubMed

    Marsden, P D; Bruce-Chwatt, L J

    1975-01-01

    Cerebral malaria is an acute diffuse encephalopathy associated only with Plasmodium falciparum. It is probably a consequence of the rapid proliferation of the parasites in the body of man in relation to red cell invasion, and results in stagnation of blood flow in cerebralcapillaries with thromobotic occlusion of large numbers of cerebral capillaries. The subsequent cerebral pathology is cerebral infarction with haemorrhage and cerebral oedema. The wide prevalence of P. falciparum in highly endemic areas results in daily challenges to patients from several infected mosquitoes. It is thus important to understand the characteristics of P. falciparum, since this is one of the most important protozoan parasites of man and severe infection from it constitutes one of the few real clinical emergencies in tropical medicine. One of the more important aspects of the practice of medicine in the tropics is to establish a good understanding of the pattern of medical practice in that area. This applies to malaria as well as to other diseases. The neophyte might be somewhat surprised to learn, for example that an experienced colleague who lives in a holoendemic malarious area such as West Africa, sees no cerebral malaria. But the explanation is simple when the doctor concerned has a practice which involves treating adults only. Cerebral malaria is rare in adults, because in highly endemic areas, by the age of 1 year most of the infants in a group under study have already experienced their first falciparum infection. By the time they reach adult life, they have a solid immunity against severe falciparum infections. In fact, "clinical malaria" could occur in such a group under only two circumstances: 1) in pregnancy, a patent infection with P. falciparum might develop, probably due to an IgG drain across the placenta to the foetus;2) in an individual who has constantly taken antimalarials and who may have an immunity at such a low level that when antimalarial therapy is interrupted

  14. SIT for African malaria vectors: Epilogue

    PubMed Central

    Townson, Harold

    2009-01-01

    As a result of increased support and the diligent application of new and conventional anti-malaria tools, significant reductions in malaria transmission are being accomplished. Historical and current evolutionary responses of vectors and parasites to malaria interventions demonstrate that it is unwise to assume that a limited suite of tools will remain effective indefinitely, thus efforts to develop new interventions should continue. This collection of manuscripts surveys the prospects and technical challenges for applying a novel tool, the sterile insect technique (SIT), against mosquitoes that transmit malaria. The method has been very successful against many agricultural pest insects in area-wide programs, but demonstrations against malaria vectors have not been sufficient to determine its potential relative to current alternatives, much of which will hinge ultimately upon cost. These manuscripts provide an overview of current efforts to develop SIT and identify key research issues that remain. PMID:19917071

  15. Problems of epidemiology in malaria eradication

    PubMed Central

    Yekutiel, P.

    1960-01-01

    With an increasing number of malaria eradication programmes approaching or entering the consolidation phase, the epidemiological features of disappearing malaria are getting better known and defined. At the same time, the old classical methods of measuring malaria prevalence have become inadequate and new methods for the epidemiological assessment of the progress of eradication are being developed. In this article the new methods of assessment and epidemiological and statistical criteria for discontinuing residual spraying and for the stability of consolidation are discussed on the basis of field experience in several countries during the past two or three years. Some prominent epidemiological features of malaria at reduced levels of transmission are described, special attention being given to the role of the asymptomatic carrier in malaria eradication. PMID:13846510

  16. 4-(1H)-Quinolones and 1,2,3,4-Tetrahydroacridin-9(10H)-ones prevent the transmission of Plasmodium falciparum to Anopheles freeborni.

    PubMed

    Sáenz, Fabián E; Lacrue, Alexis N; Cross, R Matthew; Maignan, Jordany R; Udenze, Kenneth O; Manetsch, Roman; Kyle, Dennis E

    2013-12-01

    Malaria kills approximately 1 million people a year, mainly in sub-Saharan Africa. Essential steps in the life cycle of the parasite are the development of gametocytes, as well as the formation of oocysts and sporozoites, in the Anopheles mosquito vector. Preventing transmission of malaria through the mosquito is necessary for the control of the disease; nevertheless, the vast majority of drugs in use act primarily against the blood stages. The study described herein focuses on the assessment of the transmission-blocking activities of potent antierythrocytic stage agents derived from the 4(1H)-quinolone scaffold. In particular, three 3-alkyl- or 3-phenyl-4(1H)-quinolones (P4Qs), one 7-(2-phenoxyethoxy)-4(1H)-quinolone (PEQ), and one 1,2,3,4-tetrahydroacridin-9(10H)-one (THA) were assessed for their transmission-blocking activity against the mosquito stages of the human malaria parasite (Plasmodium falciparum) and the rodent parasite (P. berghei). Results showed that all of the experimental compounds reduced or prevented the exflagellation of male gametocytes and, more importantly, prevented parasite transmission to the mosquito vector. Additionally, treatment with ICI 56,780 reduced the number of sporozoites that reached the Anopheles salivary glands. These findings suggest that 4(1H)-quinolones, which have activity against the blood stages, can also prevent the transmission of Plasmodium to the mosquito and, hence, are potentially important drug candidates to eradicate malaria.

  17. Malaria and Travelers

    MedlinePlus

    ... CDC’s Malaria Maps are another reference to help locate areas with malaria. Conduct an individualized risk assessment Prevention of malaria involves a balance between ensuring that all people who will be at risk of infection use ...

  18. Adult and child malaria mortality in India

    PubMed Central

    Dhingra, Neeraj; Jha, Prabhat; Sharma, Vinod P; Cohen, Alan A; Jotkar, Raju M; Rodriguez, Peter S; Bassani, Diego G; Suraweera, Wilson; Laxminaryan, Ramanan; Peto, Richard

    2010-01-01

    Summary Background Malaria, a non-fatal disease if detected promptly and treated properly, still causes many deaths in malaria-endemic countries with limited healthcare facilities. National malaria mortality rates are, however, particularly difficult to assess reliably in such countries, as any fevers reliably diagnosed as malaria are likely therefore to be cured. Hence, most malaria deaths are from undiagnosed malaria, which may be misattributed in retrospective enquiries to other febrile causes of death, or vice-versa. Aim To estimate plausible ranges of malaria mortality in India, the most populous country where it remains common. Methods Nationally representative retrospective study of 122,000 deaths during 2001-03 in 6671 areas. Full-time non-medical field workers interviewed families or other respondents about each death, obtaining a half-page narrative plus answers to specific questions about the severity and course of any fevers. Each field report was scanned and emailed to two of 130 trained physicians, who independently coded underlying causes, with discrepancies resolved either via anonymous reconciliation or, failing that, adjudication. Findings Of all coded deaths at ages 1 month to 70 years, 3.6% (2681/75,342) were attributed to malaria. Of these, 2419 (90%) were rural and 2311 (86%) were not in any healthcare facility. Malaria-attributed death rates correlated geographically with local malaria transmission rates derived independently from the Indian malaria control programme, and rose after the wet season began. The adjudicated results suggest 205,000 malaria deaths per year in India before age 70 (55,000 in early childhood, 30,000 at ages 5-14, 120,000 at ages 15-69); cumulative probability 1.8% of death from malaria before age 70. Plausible upper and lower bounds (